CN114306543A - Traditional Chinese medicine composition for treating Alzheimer disease and preparation method and application thereof - Google Patents
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Abstract
本发明公开一种用于治疗阿尔茨海默病的中药组合物及其制备方法和应用。所述的中药组合物由以下重量份的各原料药组成：墨早莲10‑15重量份、刘寄奴3‑8重量份、草豆蔻2‑6重量份、冬葵子5‑15重量份、香加皮2‑6重量份以及八月札10‑15重量份。该中药组合物具有补肾散瘀、健胃润肠、祛湿理气的基本功效。动物实验结果表明，中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)可改善β‑淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力、β‑淀粉样蛋白前体蛋白表达水平、白介素‑1β表达水平、乙酰胆碱代谢酶表达水平，同时对小鼠的主要脏器指数和体重无影响，说明该中药组合物治疗阿尔茨海默病有效并且无副作用。The invention discloses a traditional Chinese medicine composition for treating Alzheimer's disease and a preparation method and application thereof. Described traditional Chinese medicine composition is made up of each raw material medicine of the following parts by weight: 10-15 parts by weight of Mozao Lian, 3-8 parts by weight of Liu Jinu, 2-6 parts by weight of Cardamom, 5-15 parts by weight of Mallow Seed , 2-6 parts by weight of Xiangjiapi, and 10-15 parts by weight of August. The traditional Chinese medicine composition has the basic functions of invigorating the kidney and dispelling blood stasis, strengthening the stomach and moistening the intestines, dispelling dampness and regulating qi. The results of animal experiments showed that the high dose (12.74g/kg) and the medium dose (6.37g/kg) of the traditional Chinese medicine composition could improve the learning ability of β-amyloid-induced Alzheimer's disease Kunming mice, and the β-amyloid The expression level of protein-like precursor protein, the expression level of interleukin-1β, the expression level of acetylcholine metabolizing enzyme, and the main organ index and body weight of mice have no effect, indicating that the traditional Chinese medicine composition is effective in treating Alzheimer's disease and has no side effects.
Description
技术领域technical field
本发明涉及一种中药组合物及其制备方法和用途，特别涉及一种用于治疗阿尔茨海默病的中药组合物及其制备方法和应用。本发明属于中药研究技术领域。The present invention relates to a traditional Chinese medicine composition, a preparation method and application thereof, in particular to a traditional Chinese medicinal composition for treating Alzheimer's disease, and a preparation method and application thereof. The invention belongs to the technical field of traditional Chinese medicine research.
背景技术Background technique
阿尔茨海默病是一种常见的老年性疾病(Hampel H，Vassar R，De Strooper B，etal.The beta-Secretase BACE1 in Alzheimer's Disease[J].Biol Psychiatry，2021，89(8)：745-756.)，多与脑组织不同区域β-淀粉样蛋白含量增加有一定关系 (Busche MA，Hyman BT.Synergy between amyloid-beta and tau in Alzheimer's disease[J].NatNeurosci，2020，23(10)：1183-1193.)。β-淀粉样蛋白是阿尔茨海默病非常强大的刺激因子(Chen WT，Lu A，Craessaerts K，et al.Spatial Transcriptomics and In SituSequencing to Study Alzheimer's Disease[J].Cell，2020， 182(4)：976-991.)，会促进机体脑组织形成与炎症反应密切相关的正反馈效应环，β-淀粉样蛋白含量会继续增加(Breijyeh Z，Karaman R.Comprehensive Review on Alzheimer's Disease Causes andTreatment[J].Molecules，2020，25(24)：5789.)，不断加重脑组织的无菌性炎症反应，进而引起相应的症状及其体征。Alzheimer's disease is a common senile disease (Hampel H, Vassar R, De Strooper B, et al. The beta-Secretase BACE1 in Alzheimer's Disease [J]. Biol Psychiatry, 2021, 89(8): 745- 756.), which is mostly related to the increase of β-amyloid content in different regions of brain tissue (Busche MA, Hyman BT. Synergy between amyloid-beta and tau in Alzheimer's disease [J]. Nat Neurosci, 2020, 23(10): 1183-1193.). β-Amyloid is a very powerful stimulator of Alzheimer's disease (Chen WT, Lu A, Craessaerts K, et al.Spatial Transcriptomics and In SituSequencing to Study Alzheimer's Disease[J].Cell, 2020, 182(4) : 976-991.), will promote the formation of a positive feedback effect loop closely related to the inflammatory response in the brain tissue of the body, and the content of β-amyloid will continue to increase (Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer's Disease Causes and Treatment[J] .Molecules, 2020, 25(24): 5789.), constantly aggravating the aseptic inflammatory response of brain tissue, thereby causing corresponding symptoms and signs.
研究资料显示，阿尔茨海默病多伴有学习能力下降(Kent SA，Spires-Jones TL，Durrant CS.The physiological roles of tau and Abeta：implications forAlzheimer's disease pathology and therapeutics[J].Acta Neuropathol，2020，140(4)：417-447.)，近期发生的事情极其容易忘记，这与脑组织炎症介质含量增加并造成海马区域损伤有一定关系，也与脑组织β-淀粉样蛋白前体蛋白含量增加有一定关系，而脑组织炎症介质及其β-淀粉样蛋白前体蛋白出现异常增多，多与脑组织不同区域β-淀粉样蛋白含量正反馈增加引起学习能力下降(Roussarie JP，Yao V，Rodriguez- Rodriguez P，etal.Selective Neuronal Vulnerability in Alzheimer's Disease A Network- BasedAnalysis[J].Neuron，2020，107(5)：821-835)存在密切的相关性。Research data show that Alzheimer's disease is often associated with a decline in learning ability (Kent SA, Spires-Jones TL, Durrant CS. The physiological roles of tau and Abeta: implications for Alzheimer's disease pathology and therapeutics [J]. Acta Neuropathol, 2020, 140(4):417-447.), what happened recently is extremely easy to forget, which is related to the increase in the content of inflammatory mediators in brain tissue and causing damage to the hippocampus, as well as the increase in the content of β-amyloid precursor protein in brain tissue. There is a certain relationship, and the abnormal increase of inflammatory mediators and β-amyloid precursor protein in brain tissue is mostly related to the increase of β-amyloid protein content in different regions of brain tissue, which leads to the decline of learning ability (Roussarie JP, Yao V, Rodriguez). - Rodriguez P, et al. Selective Neuronal Vulnerability in Alzheimer's Disease A Network-Based Analysis [J]. Neuron, 2020, 107(5): 821-835) is closely related.
随着机体年龄增加，脑组织自由基的产生量也会逐渐增加，星形胶质细胞结构异常会引起血脑屏障结构异常(Serrano-Pozo A，Das S，Hyman BT.APOE and Alzheimer'sdisease advances in genetics pathophysiology and therapeutic approaches[J].Lancet Neurol，2021，20(1)：68-80.)，伴有脑组织胆碱系统失衡，乙酰胆碱代谢酶含量异常(Ren JM，Zhang SL，Wang XL，et al.Expression levels of the alpha7 nicotinicacetylcholine receptor in the brains of patients with Alzheimer's disease andtheir effect on synaptic proteins in SH-SY5Y cells[J].Mol Med Rep，2020， 22(3)：2063-2075.)，引起自由基含量继续增加(Uversky VN，Elrashdy F，Aljadawi A，etal.Severe acute respiratory syndrome coronavirus 2infection reaches the humannervous system How[J].J Neurosci Res，2021，99(3)：750-777.)，进而促发脑组织自由基的瀑布式反应，加重机体的炎症反应。As the body ages, the generation of free radicals in brain tissue will gradually increase, and the abnormal structure of astrocytes can cause abnormal structure of the blood-brain barrier (Serrano-Pozo A, Das S, Hyman BT. APOE and Alzheimer's disease advances in genetics pathophysiology and therapeutic approaches[J]. Lancet Neurol, 2021, 20(1): 68-80.), accompanied by imbalance of choline system in brain tissue and abnormal content of acetylcholine metabolizing enzymes (Ren JM, Zhang SL, Wang XL, et al.Expression levels of the alpha7 nicotinicacetylcholine receptor in the brains of patients with Alzheimer's disease and their effect on synaptic proteins in SH-SY5Y cells[J].Mol Med Rep, 2020, 22(3):2063-2075.), causing The content of free radicals continued to increase (Uversky VN, Elrashdy F, Aljadawi A, et al. Severe acute respiratory syndrome coronavirus 2infection reaches the humannervous system How[J].J Neurosci Res, 2021, 99(3): 750-777.), and then Promote the waterfall reaction of free radicals in brain tissue and aggravate the body's inflammatory response.
实际上，年老体弱者多伴有情志失调，病理性产物积聚是比较正常的生理现象，而这与小胶质细胞活化有一定关系(Bartels T，De Schepper S，Hong S.Microgliamodulate neurodegeneration in Alzheimer's and Parkinson's diseases[J].Science，2020， 370(6512)：66-69.)，小胶质细胞活化会促使白介素-1β含量增加(RahmanMA， Islam K，Rahman S，et al.Neurobiochemical Cross-talk Between COVID-19andAlzheimer's Disease[J].Mol Neurobiol，2021，58(3)：1017-1023.)，促进脑组织炎症反应，还可以促进β-淀粉样蛋白前体蛋白逐渐分解成β-淀粉样蛋白(Hur JY， Frost GR，WuX，et al.The innate immunity protein IFITM3 modulates gamma- secretase inAlzheimer's disease[J].Nature，2020，586(7831)：735-740.)，促使神经元外侧形成大量的老年斑，诱使机体脑组织病变程度加重，促进机体脑组织乙酰胆碱含量增加对阿尔茨海默病是有好处的(Lanni C，Masi M，Racchi M，et al.Cancer and Alzheimer's diseaseinverse relationship an age-associated diverging derailment of sharedpathways[J].Mol Psychiatry，2021，26(1)：280-295.)，会改善β-淀粉样蛋白诱导阿尔茨海默病，这就需要乙酰胆碱代谢酶含量降低，同时胆碱乙酰化酶含量增加。In fact, the elderly and infirm are often accompanied by emotional disorders, and the accumulation of pathological products is a relatively normal physiological phenomenon, which is related to the activation of microglia (Bartels T, De Schepper S, Hong S. Microgliamodulate neurodegeneration in Alzheimer's and Parkinson's diseases[J].Science, 2020, 370(6512): 66-69.), microglia activation can promote the increase of interleukin-1β content (Rahman MA, Islam K, Rahman S, et al. Neurobiochemical Cross-talk Between COVID-19andAlzheimer's Disease[J].Mol Neurobiol, 2021, 58(3): 1017-1023.), promotes the inflammatory response of brain tissue, and can also promote the gradual decomposition of β-amyloid precursor protein into β-amyloid (Hur JY, Frost GR, WuX, et al.The innate immunity protein IFITM3 modulates gamma-secretase in Alzheimer's disease[J].Nature, 2020, 586(7831): 735-740.), promoting the formation of a large number of senile plaques on the outside of neurons , inducing the aggravation of brain tissue lesions, and promoting the increase of acetylcholine content in brain tissue is beneficial to Alzheimer's disease (Lanni C, Masi M, Racchi M, et al. Cancer and Alzheimer's disease inverse relationship an age-associated diverging derailment of sharedpathways[J].Mol Psychiatry, 2021, 26(1): 280-295.), can improve β-amyloid-induced Alzheimer's disease, which requires the reduction of acetylcholine metabolizing enzymes, while choline acetyl The enzyme content increased.
已经证实，阿尔茨海默病脑组织的病变主要集中海马区域(Richetin K，SteulletP，Pachoud M，et al.Tau accumulation in astrocytes of the dentate gyrus inducesneuronal dysfunction and memory deficits in Alzheimer's disease[J].NatNeurosci，2020， 23(12)：1567-1579.)。海马区域通常可以分为多个神经分区，其中海马1区和海马3区与阿尔茨海默病关系极为密切(Lyssenko NN，Pratico D.ABCA7 and thealtered lipidostasis hypothesis of Alzheimer's disease[J].Alzheimers Dement，2021， 17(2)：164-174.)。海马区域自由基的产生量增加、β-淀粉样蛋白含量增加(Ruan Z，Pathak D，Venkatesan Kalavai S，et al.Alzheimer's disease brain-derivedextracellular vesicles spread tau pathology in interneurons[J].Brain，2021，144(1)：288-309.)、白介素-1β含量增加等，均可以快速诱导机体出现非常明显的症状及其体征，很多研究者多在海马1区和海马3区注射大量的β-淀粉样蛋白建立常规的阿尔茨海默病模型。It has been confirmed that the lesions of Alzheimer's disease brain tissue are mainly concentrated in the hippocampus (Richetin K, Steullet P, Pachoud M, et al. Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer's disease [J]. Nat Neurosci, 2020, 23(12):1567-1579.). The hippocampal region can usually be divided into multiple neural subregions, among which
众所周知，很多药物对β-淀粉样蛋白诱导阿尔茨海默病效果较好，包括抗β- 淀粉样蛋白药物(Lozupone M，Solfrizzi V，DUrso F，et al.Anti-amyloid-beta proteinagents for the treatment of Alzheimer's disease：an update on emerging drugs[J].Expert Opin Emerg Drugs，2020，25(3)：319-335.)、雌激素、维生素B6、维生素C(YuJT，Xu W，Tan CC，et al.Evidence-based prevention of Alzheimer's diseasesystematic review and meta-analysis of 243observational prospective studiesand 153randomised controlled trials[J].J Neurol Neurosurg Psychiatry，2020，91(11)：1201-1209.)、抗氧化剂、白藜芦醇(Han Y，Chu X，Cui L，et al.Neuronalmitochondria-targeted therapy for Alzheimer's disease by systemic delivery ofresveratrol using dual-modified novel biomimetic nanosystems[J].Drug Deliv，2020，27(1)：502-518.)、新型纳米硒等，但是很多药物具有一定的副作用。近年来，很多研究者为了克服这些副作用，于是选择副作用很小、具有整体性调节功能、靶点相对较多的药物开展防治β-淀粉样蛋白诱导阿尔茨海默病的研究。It is well known that many drugs have good effects on β-amyloid-induced Alzheimer's disease, including anti-β-amyloid drugs (Lozupone M, Solfrizzi V, DUrso F, et al. Anti-amyloid-beta proteinagents for the treatment of Alzheimer's disease: an update on emerging drugs[J].Expert Opin Emerg Drugs, 2020, 25(3): 319-335.), estrogen, vitamin B6, vitamin C (YuJT, Xu W, Tan CC, et al .Evidence-based prevention of Alzheimer's diseasesystematic review and meta-analysis of 243observational prospective studies and 153randomised controlled trials[J].J Neurol Neurosurg Psychiatry, 2020, 91(11): 1201-1209.), antioxidants, resveratrol ( Han Y, Chu X, Cui L, et al.Neuronalmitochondria-targeted therapy for Alzheimer's disease by systemic delivery ofresveratrol using dual-modified novel biomimetic nanosystems[J].Drug Deliv, 2020, 27(1):502-518.), New nano-selenium, etc., but many drugs have certain side effects. In recent years, in order to overcome these side effects, many researchers choose drugs with few side effects, overall regulatory functions, and relatively more targets to carry out research on the prevention and treatment of β-amyloid-induced Alzheimer's disease.
中医理论认为，阿尔茨海默病多为本虚标实，具体而言是肾气不足(冯奕钧，郑伟，王兴佳，等.补肾法治疗阿尔茨海默型痴呆研究进展[J].四川中医，2021，39 (2)：214-217.)，这与老年人年龄偏大有一定关系。肾气充沛则肾阳充足，学习能力较强，避免髓海空虚，有助于缓解老年人的学习能力减退，因此治疗阿尔茨海默病需要选择具有补肾的药物。老年人饮食消化功能常常较弱，致使营卫失和，肾精亏虚，神明失养(陈慧泽，谈世进，孟胜喜.中西医结合防治阿尔茨海默病的研究进展[J].中西医结合心脑血管病杂志，2021，19(12)：2025-2029.)，β-淀粉样蛋白逐渐沉积于脑组织内部，加重机体的症状及其体征，所以治疗阿尔茨海默病需要选择具有健胃润肠的药物。老年人肾气虚也，湿毒、瘀毒等逐渐堆积(张译戈，梁雨晴，李雅黎，等.从肾虚痰瘀浅谈阿尔茨海默病的中医病机演变[J].世界科学技术-中医药现代化，2021，23(1)：159-164)，这与老年人体内气机不畅，阴阳失调有一定关系(赵明，李浩，刘南阳，等.浅析升清降浊法防治老年性痴呆的理论与应用[J].环球中医药，2021，14(2)：278-281.)，进而促进海马区域自由基的产生量增加、β-淀粉样蛋白含量增加、白介素-1β含量增加等，诱发阿尔茨海默病。因此治疗阿尔茨海默病需要散瘀、祛湿。综合分析，治疗β-淀粉样蛋白诱导阿尔茨海默病需要补肾散瘀、健胃润肠、祛湿理气。According to the theory of traditional Chinese medicine, Alzheimer's disease is mostly deficiency and deficiency, specifically, the deficiency of kidney qi (Feng Yijun, Zheng Wei, Wang Xingjia, et al. Research progress in the treatment of Alzheimer's type dementia with kidney-tonifying method [J]. Sichuan Traditional Chinese Medicine) , 2021, 39 (2): 214-217.), which is related to the older age of the elderly. If the kidney qi is abundant, the kidney yang will be sufficient, and the learning ability will be strong, avoiding the void of the marrow sea and helping to relieve the learning ability decline of the elderly. Therefore, the treatment of Alzheimer's disease needs to choose drugs with kidney-tonifying. The diet and digestion function of the elderly are often weak, resulting in the disharmony of nutrition and health, deficiency of kidney essence, and loss of nourishment (Chen Huize, Tan Shijin, Meng Shengxi. Research progress in the prevention and treatment of Alzheimer's disease with integrated traditional Chinese and Western medicine [J]. Chinese and Western Medicine Combined with the Journal of Cardiovascular and Cerebrovascular Diseases, 2021, 19(12): 2025-2029.), β-amyloid is gradually deposited in the brain tissue, aggravating the symptoms and signs of the body, so the treatment of Alzheimer's disease needs to choose the Stomach and intestines medicine. In the elderly, kidney qi deficiency is also known, and damp toxin and blood stasis are gradually accumulated (Zhang Yige, Liang Yuqing, Li Yali, et al. The evolution of traditional Chinese medicine pathogenesis of Alzheimer's disease from the perspective of kidney deficiency and phlegm blood stasis [J]. World Science and Technology-China Modernization of Medicine, 2021, 23(1): 159-164), which has a certain relationship with the stagnation of qi in the elderly and the imbalance of yin and yang (Zhao Ming, Li Hao, Liu Nanyang, et al. Analysis of the prevention and treatment of the method of promoting clearness and descending turbidity The theory and application of senile dementia [J]. Universal Chinese Medicine, 2021, 14(2): 278-281.), which in turn promotes the increase in the production of free radicals in the hippocampus, the increase in the content of β-amyloid, the increase in interleukin-1β Increased content, etc., induce Alzheimer's disease. Therefore, the treatment of Alzheimer's disease requires removing blood stasis and dampness. Comprehensive analysis shows that the treatment of β-amyloid-induced Alzheimer's disease requires invigorating the kidney and dispelling blood stasis, strengthening the stomach and moistening the intestines, and removing dampness and regulating qi.
为此，本发明提供了包括6味中药材组成的中药组合物，其包括墨早莲10- 15重量份、刘寄奴3-8重量份、草豆蔻2-6重量份、冬葵子5-15重量份、香加皮 2-6重量份以及八月札10-15重量份。动物实验结果表明，本发明的中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)可改善β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力、β-淀粉样蛋白前体蛋白表达水平、白介素-1β表达水平、乙酰胆碱代谢酶表达水平，同时中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠的主要脏器指数和体重无影响，说明本发明的中药组合物可用于治疗阿尔茨海默病并且无副作用。To this end, the present invention provides a traditional Chinese medicine composition comprising 6 Chinese medicinal materials, comprising 10-15 parts by weight of Mochae lotus, 3-8 parts by weight of Liu Jinu, 2-6 parts by weight of cardamom, 5 parts by weight of Mallow -15 parts by weight, 2-6 parts by weight of incense sticks and 10-15 parts by weight of August. The results of animal experiments show that the high dose (12.74g/kg) and the medium dose (6.37g/kg) of the traditional Chinese medicine composition of the present invention can improve the learning ability of β-amyloid-induced Alzheimer's disease Kunming mice, The expression level of β-amyloid precursor protein, the expression level of interleukin-1β, the expression level of acetylcholine metabolizing enzyme, and the effect of traditional Chinese medicine composition on the main organ index and body weight of β-amyloid-induced Alzheimer's disease Kunming mice were not. It shows that the traditional Chinese medicine composition of the present invention can be used for the treatment of Alzheimer's disease and has no side effects.
发明内容SUMMARY OF THE INVENTION
本发明所要解决的技术问题是提供一种用于防治阿尔茨海默病的中药组合物及其制备方法和用途。The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for preventing and treating Alzheimer's disease and its preparation method and application.
为了达到上述目的，本发明采用了以下技术手段：In order to achieve the above object, the present invention has adopted the following technical means:
本发明的一种用于治疗阿尔茨海默病的中药组合物，其特征在于，所述的中药组合物由以下重量份的各原料药组成：墨早莲10-15重量份、刘寄奴3-8重量份、草豆蔻2-6重量份、冬葵子5-15重量份、香加皮2-6重量份以及八月札10- 15重量份。A traditional Chinese medicine composition for treating Alzheimer's disease of the present invention is characterized in that, the traditional Chinese medicine composition is composed of the following raw materials by weight: 10-15 3-8 parts by weight, 2-6 parts by weight of cardamom, 5-15 parts by weight of mallow seeds, 2-6 parts by weight of fragrant peel, and 10-15 parts by weight of August.
其中，墨早莲，别名旱莲草，性寒，味酸、味甘，归属于肾经、肝经，具有补肾、凉血、滋肝、止血的基本功效；刘寄奴，别名六月雪，性微温，味苦、味辛，归属于脾经、心经、肝经，具有散瘀、通经、化积、止痛、破血、消食的基本功效；草豆蔻，别名草蔻仁，性温，味辛，归属于胃经、脾经，具有健胃、消痞、燥湿、温中的基本功效；冬葵子，性寒，味甘，归属于小肠经、大肠经、膀胱经，具有润肠、通淋、利水、下乳的基本功效；香加皮，别名杠柳皮，性微温，味苦、味辛，归属于心经、肾经、肝经，具有祛湿、强筋、利水、祛风、消肿、壮骨的基本功效；八月札，性寒，味甘、味苦，归属于肾经、脾经、肝经，具有理气、止痛、疏肝、活血的基本功效。在本发明的中药组合物中，君药墨早莲、刘寄奴，具有补肾散瘀的基本功效；臣药草豆蔻、冬葵子，具有健胃润肠的基本功效；佐药香加皮，具有祛湿的基本功效；使药八月札，具有理气的基本功效。诸药配伍能够产生补肾散瘀、健胃润肠、祛湿理气的功效。Among them, Mo Zaolian, alias Eclipta, is cold in nature, tastes sour and sweet, belongs to the kidney meridian and liver meridian, and has the basic effects of tonifying the kidney, cooling blood, nourishing the liver, and stopping bleeding; Liu Jinu, alias June Snow , slightly warm in nature, bitter and pungent in taste, belonging to the spleen meridian, heart meridian and liver meridian, with the basic effects of dispersing blood stasis, clearing meridians, dissolving accumulation, relieving pain, breaking blood, and digestion; , pungent in taste, belonging to the stomach and spleen meridians, and has the basic effects of strengthening the stomach, eliminating phlegm, drying dampness, and warming the middle; The basic functions of moistening the intestines, clearing the stranguria, inducing water, and lowering the milk; Xiangjiapi, also known as the bark willow, is slightly warm in nature, bitter in taste, and acrid in taste. It belongs to the heart, kidney, and liver meridians. , the basic effect of dispelling wind, reducing swelling and strengthening bones; August sclera, cold in nature, sweet and bitter in taste, belonging to the kidney meridian, spleen meridian and liver meridian, and has the basic effects of regulating qi, relieving pain, soothing liver and promoting blood circulation. In the traditional Chinese medicine composition of the present invention, the king herbs Mozaolian and Liu Jinu have the basic effect of invigorating the kidney and dispelling blood stasis; the minister herbs cardamom and mallow seed have the basic effect of strengthening the stomach and moistening the intestines; It has the basic effect of dispelling dampness; it has the basic effect of regulating Qi. The compatibility of various medicines can produce the effects of invigorating the kidney and dispelling blood stasis, strengthening the stomach and moistening the intestines, dispelling dampness and regulating qi.
其中，优选的，所述的中药组合物由以下重量份的各原料药组成：墨早莲12.5 重量份、刘寄奴6重量份、草豆蔻4重量份、冬葵子10重量份、香加皮4.5重量份以及八月札12重量份。Wherein, preferably, the described Chinese medicine composition is made up of the following raw materials by weight: 12.5 parts by weight of Mozao Lian, 6 parts by weight of Liu Jinu, 4 parts by weight of Cardamom, 10 parts by weight of Mallow Seed, 4.5 parts by weight of leather and 12 parts by weight of August.
行为学测试实验结果表明，与不给药对照组比较，模型验证组昆明小鼠潜伏期明显延长(P＜0.05)，模拟手术组昆明小鼠潜伏期改变不明显(P＞0.05)；与模型验证组比较，西药干预组、中药组合物高剂量组、中药组合物中剂量组昆明小鼠潜伏期明显缩短(P＜0.05)，中药组合物低剂量组昆明小鼠潜伏期改变不明显(P＞0.05)，说明中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37 g/kg)可以改善β-淀粉样蛋白诱导阿尔茨海默病清洁级昆明小鼠模型的学习记忆能力。The experimental results of behavioral test showed that compared with the control group without drug administration, the latency period of Kunming mice in the model validation group was significantly prolonged (P<0.05), while the latency period of Kunming mice in the simulated operation group did not change significantly (P>0.05). In comparison, the incubation period of Kunming mice in western medicine intervention group, high-dose group of traditional Chinese medicine composition, and medium-dose group of traditional Chinese medicine composition was significantly shortened (P<0.05), and the incubation period of Kunming mice in low-dose group of traditional Chinese medicine composition was not significantly changed (P>0.05). The results indicated that the high dose (12.74 g/kg) and the medium dose (6.37 g/kg) of the traditional Chinese medicine composition could improve the learning and memory ability of the β-amyloid-induced Alzheimer's disease clean-grade Kunming mouse model.
酶联免疫吸附实验结果表明，与不给药对照组比较，模型验证组昆明小鼠β- 淀粉样蛋白前体蛋白含量明显增加(P＜0.05)且白介素-1β含量明显增加(P＜ 0.05)，模拟手术组昆明小鼠β-淀粉样蛋白前体蛋白含量和白介素-1β含量改变不明显(P＞0.05)；与模型验证组比较，西药干预组、中药组合物高剂量组、中药组合物中剂量组昆明小鼠β-淀粉样蛋白前体蛋白含量和白介素-1β含量明显降低 (P＜0.05)，组合物低剂量组昆明小鼠β-淀粉样蛋白前体蛋白含量和白介素-1β含量改变不明显(P＞0.05)，说明中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)可以改善β-淀粉样蛋白诱导阿尔茨海默病清洁级昆明小鼠模型的β-淀粉样蛋白前体蛋白含量和白介素-1β含量，提示中药组合物高剂量(12.74 g/kg)、中药组合物中剂量(6.37g/kg)可以改善β-淀粉样蛋白诱导阿尔茨海默病清洁级昆明小鼠模型炎症介质水平及其减少老年斑沉积，这与减弱小胶质细胞及星形胶质细胞活化水平有关。The results of enzyme-linked immunosorbent assay showed that compared with the control group without drug administration, the content of β-amyloid precursor protein and the content of interleukin-1β in Kunming mice in the model validation group were significantly increased (P＜0.05) and the content of interleukin-1β was significantly increased (P＜0.05). , the content of β-amyloid protein precursor protein and interleukin-1β content of Kunming mice in the simulated operation group did not change significantly (P>0.05); The content of β-amyloid precursor protein and the content of interleukin-1β in Kunming mice in the middle-dose group were significantly decreased (P<0.05), while the content of β-amyloid precursor protein and the content of interleukin-1β in Kunming mice in the low-dose group of the composition The change was not obvious (P>0.05), indicating that the high dose of the traditional Chinese medicine composition (12.74g/kg) and the medium dose of the traditional Chinese medicine composition (6.37g/kg) can improve the β-amyloid-induced Alzheimer's disease. The content of β-amyloid precursor protein and the content of interleukin-1β in the mouse model suggested that the high dose of traditional Chinese medicine composition (12.74 g/kg) and the medium dose of traditional Chinese medicine composition (6.37 g/kg) could improve the induction of β-amyloid. Levels of inflammatory mediators and their reduction in senile plaque deposition in a clean-grade Kunming mouse model of Alzheimer's disease, which are associated with attenuated levels of microglia and astrocyte activation.
免疫组化和基因检测结果表明，与不给药对照组比较，模型验证组昆明小鼠乙酰胆碱代谢酶蛋白和基因表达量明显增加(P＜0.05)，胆碱乙酰化酶蛋白和基因表达量明显减少(P＜0.05)，模拟手术组昆明小鼠乙酰胆碱代谢酶和胆碱乙酰化酶蛋白和基因表达量改变不明显(P＞0.05)；与模型验证组比较，西药干预组、中药组合物高剂量组、中药组合物中剂量组昆明小鼠乙酰胆碱代谢酶蛋白和基因表达量明显减少(P＜0.05)，胆碱乙酰化酶蛋白和基因表达量明显增加(P＜0.05)，组合物低剂量组昆明小鼠乙酰胆碱代谢酶和胆碱乙酰化酶蛋白和基因表达量改变不明显(P＞0.05)，说明机体脑组织胆碱乙酰化酶、机体脑组织乙酰胆碱代谢酶表达异常会引起机体脑组织乙酰胆碱含量异常，干预机体脑组织胆碱乙酰化酶、机体脑组织乙酰胆碱代谢酶表达，有助于中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)改善β-淀粉样蛋白诱导阿尔茨海默病。The results of immunohistochemistry and gene detection showed that compared with the control group without drug administration, the expression of acetylcholine metabolizing enzyme protein and gene in Kunming mice in the model validation group increased significantly (P<0.05), and the expression of choline acetylase protein and gene was significantly increased (P<0.05). Compared with the model validation group, the western medicine intervention group and the traditional Chinese medicine composition were higher The expression of acetylcholine metabolizing enzyme protein and gene in Kunming mice in the dose group and the medium-dose group of the traditional Chinese medicine composition decreased significantly (P<0.05), while the protein and gene expression of choline acetylase increased significantly (P<0.05). The protein and gene expression of acetylcholine metabolizing enzyme and choline acetylase in Kunming mice in the Kunming group did not change significantly (P>0.05), indicating that abnormal expression of choline acetylase and acetylcholine metabolizing enzyme in brain tissue could cause brain tissue abnormality. Abnormal acetylcholine content, interfering with the expression of choline acetylase and acetylcholine metabolizing enzyme in the brain tissue of the body, helps the high dose of the traditional Chinese medicine composition (12.74g/kg) and the medium dose of the traditional Chinese medicine composition (6.37g/kg) to improve beta - Amyloid induces Alzheimer's disease.
评估中药组合物改善β-淀粉样蛋白诱导阿尔茨海默病的副作用，这与评估体重和脏器指数有关。结果表明，与不给药对照组比较，模型验证组与模拟手术组昆明小鼠重要器官心、肺、肾、肝指数和体重改变不明显。经过中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)、中药组合物低剂量(3.19g/kg) 治疗后，各组昆明小鼠重要器官心、肺、肾、肝指数和体重改变不明显，说明中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)、中药组合物低剂量(3.19g/kg)治疗β-淀粉样蛋白诱导阿尔茨海默病清洁级昆明小鼠没有副作用。Evaluation of traditional Chinese medicine composition in improving the side effects of beta-amyloid-induced Alzheimer's disease, which is related to the evaluation of body weight and organ index. The results showed that compared with the control group without administration, the key organs of the Kunming mice in the model validation group and the simulated operation group did not change significantly in the heart, lung, kidney, liver index and body weight. After treatment with high dose of traditional Chinese medicine composition (12.74g/kg), medium dose of traditional Chinese medicine composition (6.37g/kg), and low dose of traditional Chinese medicine composition (3.19g/kg), the vital organs of the Kunming mice in each group of heart, lung, The kidney, liver index and body weight did not change significantly, indicating that the high dose of the traditional Chinese medicine composition (12.74g/kg), the medium dose of the traditional Chinese medicine composition (6.37 g/kg), and the low dose of the traditional Chinese medicine composition (3.19 g/kg) were used to treat β-amyloid. Like protein-induced Alzheimer's disease in clean-grade Kunming mice without side effects.
综上所述，由6味原药材墨组成的中药组合物可以有效治疗β-淀粉样蛋白诱导阿尔茨海默病且无副作用。In conclusion, the traditional Chinese medicine composition composed of six original medicinal materials ink can effectively treat β-amyloid-induced Alzheimer's disease without side effects.
进一步的，本发明还提出了所述的中药组合物在制备防治阿尔茨海默病的药物中的应用。Further, the present invention also proposes the application of the traditional Chinese medicine composition in preparing a medicine for preventing and treating Alzheimer's disease.
其中，优选的，所述的阿尔茨海默病是由β-淀粉样蛋白诱导产生的。Among them, preferably, the Alzheimer's disease is induced by β-amyloid.
更进一步的，本发明还提出了一种制备所述的中药组合物的方法，包括以下步骤：Further, the present invention also proposes a method for preparing the traditional Chinese medicine composition, comprising the following steps:
(1)按照以上所述的重量份称取各原料药，将各原料药混合均匀后，加入药物重量20-30倍的蒸馏水，浸泡2.5-3.5h后，煎煮2.5-3.5h，冷却；(1) Weigh each bulk drug according to the above-mentioned weight portion, after mixing each bulk drug uniformly, add distilled water of 20-30 times the weight of the drug, soak for 2.5-3.5h, decoct for 2.5-3.5h, and cool;
(2)将步骤(1)冷却后的药液用纱布过滤，得到第一次滤液；(2) the medicinal liquid after step (1) cooling is filtered with gauze to obtain the first filtrate;
(3)步骤(2)剩余的药物残渣，重复步骤(1)和(2)得到第二次滤液，合并二次滤液；(3) the remaining drug residues of step (2), repeat steps (1) and (2) to obtain the second filtrate, and merge the second filtrate;
(4)合并第一次滤液和第二次滤液，使用干燥箱60-70℃烘烤6-8天，获得中药组合物干膏；(4) combining the first filtrate and the second filtrate, and baking at 60-70° C. for 6-8 days in a drying oven to obtain a dry paste of the traditional Chinese medicine composition;
(5)将得到的干膏放在粉碎机内粉碎，得到所述中药组合物的干粉。(5) pulverizing the obtained dry paste in a pulverizer to obtain the dry powder of the Chinese medicine composition.
其中，优选的，步骤(2)中所述的用纱布过滤是指依次用3层纱布过滤、5 层纱布过滤、8层纱布过滤、10层纱布过滤。Wherein, preferably, filtering with gauze described in step (2) refers to filtering with 3 layers of gauze, 5 layers of gauze, 8 layers of gauze, and 10 layers of gauze in sequence.
更进一步的，本发明还提出了一种临床上适宜的用于治疗阿尔茨海默病的中药制剂，其由以上所述的中药组合物加入制剂成型所需的辅料，按照制备药物制剂的常规方法制成。Further, the present invention also proposes a clinically suitable traditional Chinese medicine preparation for the treatment of Alzheimer's disease, which is prepared by adding the above-mentioned traditional Chinese medicine composition to the auxiliary materials required for preparation molding, according to the conventional preparation of pharmaceutical preparations. method made.
其中，优选的，所述的制剂为粉剂、水煎剂、胶囊剂、丸剂、颗粒剂、片剂或口服液。Among them, preferably, the preparation is powder, decoction, capsule, pill, granule, tablet or oral liquid.
相较于现有技术，本发明的有益效果是：Compared with the prior art, the beneficial effects of the present invention are:
本发明公开了一种用于治疗阿尔茨海默病，特别是β-淀粉样蛋白诱导的阿尔茨海默病的中药组合物及其制备方法及应用。本发明的中药组合物基本组成包括 6味中药，分别是墨早莲、刘寄奴、草豆蔻、冬葵子、香加皮、八月札。本发明的中药组合物具有补肾散瘀、健胃润肠、祛湿理气的基本功效。动物实验结果表明，中药组合物高剂量(12.74g/kg)、中药组合物中剂量(6.37g/kg)可改善β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力、β-淀粉样蛋白前体蛋白表达水平、白介素-1β表达水平、乙酰胆碱代谢酶表达水平，同时中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠的主要脏器指数和体重无影响，说明本发明的中药组合物治疗阿尔茨海默病有效并且无副作用。The invention discloses a traditional Chinese medicine composition for treating Alzheimer's disease, in particular β-amyloid-induced Alzheimer's disease, and a preparation method and application thereof. The basic composition of the traditional Chinese medicine composition of the present invention includes 6 traditional Chinese medicines, which are respectively Mozaolian, Liu Jinu, Cardamom, Mallow, Xiangjiapi and August. The traditional Chinese medicine composition of the invention has the basic functions of invigorating the kidney and dispelling blood stasis, strengthening the stomach and moistening the intestines, and dispelling dampness and regulating qi. The results of animal experiments showed that the high dose (12.74g/kg) and the medium dose (6.37g/kg) of the traditional Chinese medicine composition could improve the learning ability of β-amyloid-induced Alzheimer's disease Kunming mice, β-amyloid The expression level of protein precursor protein, the expression level of interleukin-1β, the expression level of acetylcholine metabolizing enzyme, and the traditional Chinese medicine composition had no effect on the main organ index and body weight of β-amyloid-induced Alzheimer's disease Kunming mice, indicating that The traditional Chinese medicine composition of the present invention is effective in treating Alzheimer's disease and has no side effects.
附图说明Description of drawings
图1为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力的影响；Figure 1 shows the effects of traditional Chinese medicine compositions on the learning ability of β-amyloid-induced Alzheimer's disease Kunming mice;
注：横坐标是组别；纵坐标是潜伏期(s)；Note: the abscissa is the group; the ordinate is the incubation period (s);
图2为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠β-淀粉样蛋白前体蛋白含量的影响；Figure 2 shows the effect of traditional Chinese medicine compositions on the content of β-amyloid precursor protein in Kunming mice with β-amyloid induced Alzheimer's disease;
注：横坐标是组别；纵坐标是β-淀粉样蛋白前体蛋白(ng/L)；Note: the abscissa is the group; the ordinate is the β-amyloid precursor protein (ng/L);
图3为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠白介素-1β含量的影响；Fig. 3 is the effect of traditional Chinese medicine composition on the content of interleukin-1β in Kunming mice with Alzheimer's disease induced by β-amyloid;
注：横坐标是组别；纵坐标是白介素-1β(pg/mL)；Note: the abscissa is the group; the ordinate is the interleukin-1β (pg/mL);
图4为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶含量的影响；Fig. 4 is the effect of traditional Chinese medicine composition on the content of choline acetylase in Kunming mice with Alzheimer's disease induced by beta-amyloid;
注：横坐标是组别；纵坐标是胆碱乙酰化酶(平均光密度值)；Note: the abscissa is the group; the ordinate is the choline acetylase (average optical density value);
图5为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶的影响；Fig. 5 is the effect of traditional Chinese medicine composition on β-amyloid-induced Alzheimer's disease Kunming mice acetylcholine metabolizing enzyme;
注：横坐标是组别；纵坐标是乙酰胆碱代谢酶(平均光密度值)；Note: the abscissa is the group; the ordinate is the acetylcholine metabolizing enzyme (average optical density value);
图6为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶基因的影响；Fig. 6 is the effect of traditional Chinese medicine composition on β-amyloid-induced Alzheimer's disease Kunming mice choline acetylase gene;
注：横坐标是组别；纵坐标是胆碱乙酰化酶(基因表达量)；Note: the abscissa is the group; the ordinate is the choline acetylase (gene expression);
图7为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶基因的影响；Fig. 7 is the effect of traditional Chinese medicine composition on β-amyloid-induced Alzheimer's disease Kunming mice acetylcholine metabolizing enzyme gene;
注：横坐标是组别；纵坐标是乙酰胆碱代谢酶(基因表达量)；Note: the abscissa is the group; the ordinate is the acetylcholine metabolizing enzyme (gene expression);
图8为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠心指数、肺指数的影响；Fig. 8 is the effect of traditional Chinese medicine composition on the heart index and lung index of β-amyloid-induced Alzheimer's disease Kunming mice;
注：横坐标是组别；纵坐标是心指数、肺指数(mg/g)；Note: the abscissa is the group; the ordinate is the heart index, lung index (mg/g);
图9为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠肾指数、肝指数的影响；Fig. 9 is the effect of traditional Chinese medicine composition on the kidney index and liver index of β-amyloid-induced Alzheimer's disease Kunming mice;
注：横坐标是组别；纵坐标是肾指数、肝指数(mg/g)；Note: the abscissa is the group; the ordinate is the kidney index, liver index (mg/g);
图10为中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠体重的影响；Figure 10 is the effect of traditional Chinese medicine composition on the body weight of β-amyloid-induced Alzheimer's disease Kunming mice;
注：横坐标是组别；纵坐标是0天、14天、28天昆明小鼠体重(g)。Note: the abscissa is the group; the ordinate is the body weight (g) of Kunming mice at 0 days, 14 days and 28 days.
具体实施方式Detailed ways
下面进一步描述本发明，本描述中介绍的实施案例仅是范例性的，并不对本发明的范围构成限制。本专业技术人员应该理解的是，在不偏离本发明原理和方法的情况下，对本发明技术方案的细节和形式进行部分修改或替换，但基于此修改或替换均属于本发明的保护范围内。The present invention is further described below. The implementation cases introduced in this description are only exemplary and do not limit the scope of the present invention. It should be understood by those skilled in the art that, without departing from the principles and methods of the present invention, the details and forms of the technical solutions of the present invention may be partially modified or replaced, but based on this modification or replacement, all fall within the protection scope of the present invention.
实施例1一种用于防治阿尔茨海默病的中药组合物的制备Embodiment 1 A kind of preparation of traditional Chinese medicine composition for preventing and treating Alzheimer's disease
所述的中药组合物由以下重量的各原料药组成：墨早莲12.5g、刘寄奴6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札12g。The traditional Chinese medicine composition is composed of the following raw materials: 12.5g of Mozaolian, 6g of Liu Jinu, 4g of Cardamom, 10g of Mallow, 4.5g of Xiangjiapi, and 12g of August.
实施例2一种用于防治阿尔茨海默病的中药组合物的制备Embodiment 2 A kind of preparation of traditional Chinese medicine composition for preventing and treating Alzheimer's disease
所述的中药组合物由以下重量的各原料药组成：墨早莲10g、刘寄奴8g、草豆蔻3g、冬葵子8g、香加皮6g以及八月札15g。The traditional Chinese medicine composition is composed of the following raw materials: 10g of Mozaolian, 8g of Liu Jinu, 3g of Cardamom, 8g of Mallow, 6g of Xiangjiapi and 15g of August.
实施例3一种用于防治阿尔茨海默病的中药组合物的制备Embodiment 3 A kind of preparation of traditional Chinese medicine composition for preventing and treating Alzheimer's disease
所述的中药组合物由以下重量的各原料药组成：墨早莲15g、刘寄奴5g、草豆蔻5g、冬葵子15g、香加皮4g以及八月札10g。The traditional Chinese medicine composition is composed of the following raw material medicines: 15g of Mozaolian, 5g of Liu Jinu, 5g of Cardamom, 15g of Mallow, 4g of Fragrant Root and 10g of Augustus.
实施例4一种用于防治阿尔茨海默病的中药组合物(干粉)的制备Embodiment 4 A kind of preparation of traditional Chinese medicine composition (dry powder) for preventing and treating Alzheimer's disease
(1)墨早莲12.5g、刘寄奴6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札12g，每份49g，需要购买5份，一共245g。(1) Mozao Lian 12.5g, Liu Jinu 6g, Cardamom 4g, Mallow Seed 10g, Xiangjiapi 4.5g, August 12g, each 49g, you need to buy 5 servings, a total of 245g.
(2)将墨早莲、刘寄奴、草豆蔻、冬葵子、香加皮、八月札的中药组合物245g，放入20000mL大容量圆底烧瓶(蒸馏水6000mL)中浸泡3小时，然后煎煮3小时，3层纱布过滤、5层纱布过滤、8层纱布过滤、10层纱布过滤，获得第一次滤液。(2) Put 245g of the traditional Chinese medicine composition of Mozaolian, Liu Jinu, Cardamom, Mallow, Fragrantia, and August into a 20,000-mL large-capacity round-bottom flask (distilled water 6,000 mL) for 3 hours, and then soak it for 3 hours. Decoction for 3 hours, 3 layers of gauze filtration, 5 layers of gauze filtration, 8 layers of gauze filtration, and 10 layers of gauze filtration to obtain the first filtrate.
(3)将药物残渣放入20000mL大容量圆底烧瓶(蒸馏水6000mL)中浸泡3 小时，然后煎煮3小时，3层纱布过滤、5层纱布过滤、8层纱布过滤、10层纱布过滤，获得第二次滤液。(3) put the drug residue into a 20000mL large-capacity round-bottomed flask (distilled water 6000mL) for 3 hours, then decoct for 3 hours, filter with 3 layers of gauze, 5 layers of gauze, 8 layers of gauze, and 10 layers of gauze to obtain Second filtrate.
(4)合并第一次滤液及第二次滤液，使用干燥箱(65℃)烘烤7天，获得中药组合物干膏68.35g。(4) Combine the first filtrate and the second filtrate, bake in a drying oven (65° C.) for 7 days, and obtain 68.35 g of dry paste of the traditional Chinese medicine composition.
(5)将中药组合物干膏68.35g放入粉碎机内粉碎，获得中药组合物干粉 65.24g。(5) 68.35g of dry paste of traditional Chinese medicine composition was put into pulverizer and pulverized to obtain 65.24g of dry powder of traditional Chinese medicine composition.
(6)分装中药组合物干粉65.24g，每袋10g，最后一袋5.24g。-80℃冰箱保存。(6) Distribute 65.24g dry powder of traditional Chinese medicine composition, each bag is 10g, and the last bag is 5.24g. -80 ℃ refrigerator storage.
实施例5本发明的中药组合物在治疗阿尔茨海默病中的用途Example 5 Use of Chinese medicinal composition of the present invention in the treatment of Alzheimer's disease
1实验材料1 Experimental material
1.1实验动物及其仪器1.1 Experimental animals and their instruments
昆明小鼠56只(SCXK(京)2012-0001)，体重(19.6857±0.6887)g，清洁级，雄性，北京维通利华公司，常规饲养于黑龙江中医药大学实验动物中心。培养箱，上海五久公司，型号BC-J160S；电子天平，青岛精诚公司，型号JC-TP；脑立体定位仪，河北慧采公司，型号ZH-C；水迷宫，淮北正华公司，型号MWM101；彩色分析系统，武汉千屏公司，型号HMIAS；离心机，上海安亭公司，型号TGL-16G，其他仪器由张英博副教授提供。Fifty-six Kunming mice (SCXK (Beijing) 2012-0001), body weight (19.6857±0.6887) g, clean grade, male, Beijing Weitong Lihua Company, were routinely raised in the Experimental Animal Center of Heilongjiang University of Traditional Chinese Medicine. Incubator, Shanghai Wujiu Company, model BC-J160S; electronic balance, Qingdao Jingcheng Company, model JC-TP; brain stereotaxic instrument, Hebei Huicai Company, model ZH-C; water maze, Huaibei Zhenghua Company, model MWM101 ; Color analysis system, Wuhan Qianping Company, model HMIAS; centrifuge, Shanghai Anting Company, model TGL-16G, and other instruments provided by Associate Professor Zhang Yingbo.
1.2实验药品及其试剂1.2 Experimental drugs and their reagents
墨早莲12.5g、刘寄奴6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札 12g，购买于黑龙江中医药大学第一附属医院，田明对墨早莲12.5g、刘寄奴 6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札12g进行鉴定，栗明分析墨早莲12.5g、刘寄奴6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札12g可以配伍使用。盐酸多奈哌齐片，卫材药业公司；β-淀粉样蛋白前体蛋白、白介素- 1β试剂盒，南京建成公司；乙酰胆碱代谢酶、胆碱乙酰化酶，美国Santa公司；其他试剂由张英博副教授提供。Mo Zaolian 12.5g, Liu Ji Nu 6g, Cardamom 4g, Mallow Seed 10g, Xiangjia Pi 4.5g, August Zha 12g, purchased from the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Tian Ming treated Mo Zaolian 12.5g , Liu Jinu 6g, grass cardamom 4g, mallow seeds 10g, fragrant peel 4.5g, August 12g for identification, Li Ming analyzed Mozaolian 12.5g, Liu Jinu 6g, grass cardamom 4g, mallow seeds 10g , Xiangjiapi 4.5g, August 12g can be used together. Donepezil Hydrochloride Tablets, Eisai Pharmaceutical Company; β-amyloid precursor protein, interleukin-1β kit, Nanjing Jiancheng Company; .
2实验方法2 Experimental methods
2.1实验动物分组及其模型制备2.1 Experimental animal grouping and model preparation
昆明小鼠56只，随机分为不给药对照组、模拟手术组、模型验证组、西药干预组、组合物低剂量组、组合物中剂量组、组合物高剂量组，每组8只。使用β-淀粉样蛋白1-42海马注射及其猫吓鼠方法制备β-淀粉样蛋白诱导阿尔茨海默病模型，每天上午对模型验证组、西药干预组、组合物低剂量组、组合物中剂量组、组合物高剂量组进行β-淀粉样蛋白1-42海马(80pmol/μL)注射，模拟手术组注射无菌生理盐水，不给药对照组不做干预，持续20天。每天下午对模型验证组、西药干预组、组合物低剂量组、组合物中剂量组、组合物高剂量组采用猫吓鼠方法进行干预，不给药对照组与模拟手术组不采用猫吓鼠方法，持续 20天。Fifty-six Kunming mice were randomly divided into no-administration control group, simulated operation group, model validation group, western medicine intervention group, low-dose composition group, medium-dose composition group, and high-dose composition group, with 8 mice in each group. The β-amyloid - induced Alzheimer's disease model was prepared by β-amyloid 1-42 hippocampal injection and its cat-scare-mouse method. The model validation group, western medicine intervention group, low-dose composition group, and composition group were tested every morning. The middle-dose group and the high-dose composition group were injected with β-amyloid 1-42 (80pmol/μL) in the hippocampus, the simulated operation group was injected with sterile normal saline, and the no-administration control group received no intervention for 20 days. Every afternoon, the model validation group, western medicine intervention group, low-dose composition group, medium-dose composition group, and high-dose composition group were intervened by the cat-scare-mouse method, and the control group without administration and the simulated operation group did not use the cat-scare-mouse method. method for 20 days.
2.2中药组合物干粉2.2 Dry powder of traditional Chinese medicine composition
同实施例4。Same as Example 4.
2.3计算给药剂量及其动物给药2.3 Calculation of the administered dose and its animal administration
按照0.0026：1计算给药剂量，中药组合物墨早莲12.5g、刘寄奴6g、草豆蔻4g、冬葵子10g、香加皮4.5g、八月札12g，合计49g，中药组合物的给药剂量是49g*0.0026*50＝6.37g/kg，中药组合物中剂量为6.37g/kg，中药组合物高剂量为12.74g/kg，中药组合物低剂量为3.19g/kg。多奈哌齐的给药剂量为 0.001g/kg。不给药对照组、模拟手术组、模型验证组给予等量生理盐水进行灌胃；西药干预组给予0.001g/kg多奈哌齐进行灌胃；组合物低剂量组给予 3.19g/kg进行灌胃；组合物中剂量组给予6.37g/kg进行灌胃；组合物高剂量组给予12.74g/kg进行灌胃。给药持续时间为28天。Calculate the dosage according to 0.0026:1, the traditional Chinese medicine composition Mozaolian 12.5g, Liu Jinu 6g, 4g cardamom, 10g mallow seed, 4.5g Xiangjiapi, 12g August zha, a total of 49g, the total amount of the traditional Chinese medicine composition is 49g. The administration dose is 49g*0.0026*50=6.37g/kg, the middle dose of the traditional Chinese medicine composition is 6.37g/kg, the high dose of the traditional Chinese medicine composition is 12.74g/kg, and the low dose of the traditional Chinese medicine composition is 3.19g/kg. Donepezil was administered at a dose of 0.001 g/kg. The control group, the simulated operation group, and the model validation group were given the same amount of normal saline for gavage; the western medicine intervention group was given 0.001g/kg donepezil for gavage; the low-dose composition group was given 3.19g/kg for gavage; the combination The medium-dose group was given 6.37 g/kg for gavage; the high-dose group was given 12.74 g/kg for gavage. The duration of dosing was 28 days.
2.4评估动物学习能力2.4 Assessing Animal Learning Ability
使用水迷宫评估各组昆明小鼠的学习能力，昆明小鼠用墨汁着色头部，始终保持水迷宫内外参照物一致，在水迷宫第I、II、III象限进行维持4天的训练时间，每次60秒，第5天计算各组昆明小鼠的潜伏期，评估评估动物学习能力。A water maze was used to evaluate the learning ability of Kunming mice in each group. Kunming mice colored their heads with ink, and kept the internal and external reference objects consistent in the water maze. The training time was maintained in quadrants I, II and III of the water maze for 4 days. On the 5th day, the incubation period of Kunming mice in each group was calculated, and the learning ability of the animals was evaluated.
2.5评估β-淀粉样蛋白前体蛋白及白介素-1β表达水平2.5 Assess the expression levels of β-amyloid precursor protein and interleukin-1β
水迷宫评估各组昆明小鼠的学习能力后，抓取昆明小鼠，无菌下取材全脑，剥离出海马，匀浆离心，取上清液，450nm波长处使用酶标仪分析吸光度值(OD)，进一步评估β-淀粉样蛋白前体蛋白及白介素-1β表达水平。After evaluating the learning ability of Kunming mice in each group by water maze, the Kunming mice were grabbed, the whole brain was taken under aseptic conditions, the hippocampus was stripped, homogenized and centrifuged, the supernatant was taken, and the absorbance value was analyzed using a microplate reader at a wavelength of 450 nm ( OD) to further evaluate the expression levels of β-amyloid precursor protein and interleukin-1β.
2.6评估乙酰胆碱代谢酶、胆碱乙酰化酶蛋白水平2.6 Assess the protein levels of acetylcholine metabolizing enzymes and choline acetylase
实验人员戴上手套，水迷宫评估各组昆明小鼠的学习能力后，抓取昆明小鼠，昆明小鼠心脏灌注生理盐水90mL后，匀速灌注4％多聚甲醛约50mL，经过常规石蜡切片处理后，按照试剂盒基本方法测定乙酰胆碱代谢酶、胆碱乙酰化酶含量。The experimenter put on gloves, and after evaluating the learning ability of Kunming mice in each group by water maze, grabbed the Kunming mice. After the Kunming mice were perfused with 90 mL of normal saline, about 50 mL of 4% paraformaldehyde was perfused at a constant rate, and processed by conventional paraffin sections. Afterwards, the content of acetylcholine metabolizing enzyme and choline acetylase was determined according to the basic method of the kit.
2.7评估乙酰胆碱代谢酶、胆碱乙酰化酶基因水平2.7 Assess the gene levels of acetylcholine metabolizing enzymes and choline acetylase
实验人员戴上手套，水迷宫评估各组昆明小鼠的学习能力后，抓取昆明小鼠，取材全脑及其海马，提取乙酰胆碱代谢酶、胆碱乙酰化酶mRNA，反转录成cDNA，设计针对乙酰胆碱代谢酶、胆碱乙酰化酶的引物，设置针对乙酰胆碱代谢酶、胆碱乙酰化酶的反应参数，包括50℃经过反应2min，95℃经过反应 10min，95℃经过反应15s，60℃经过反应1min，经理42个基本循环，使用仪器测定乙酰胆碱代谢酶、胆碱乙酰化酶基因表达水平。The experimenter put on gloves and evaluated the learning ability of Kunming mice in each group by water maze, grabbed Kunming mice, took the whole brain and hippocampus, extracted acetylcholine metabolizing enzyme, choline acetylase mRNA, reverse transcribed into cDNA, Design primers for acetylcholine metabolizing enzyme and choline acetylase, and set reaction parameters for acetylcholine metabolizing enzyme and choline acetylase, including 50°C for 2 minutes, 95°C for 10 minutes, 95°C for 15s, and 60°C for 10 minutes. After 1 min of reaction, 42 basic cycles were conducted, and the gene expression levels of acetylcholine metabolizing enzymes and choline acetylating enzymes were measured by instruments.
2.8评估脏器指数及体重2.8 Evaluation of organ index and body weight
水迷宫评估各组昆明小鼠的学习能力后，抓取昆明小鼠，称量各组昆明小鼠0天、14天、28天体重，断头处死，取材昆明小鼠心脏、肺脏、肾脏、肝脏，按照公式计算肝指数、肾指数、心指数、肺指数。肝指数、肾指数、心指数、肺指数计算公式：心脏、肺脏、肾脏、肝脏的脏器指数(mg/g)＝心脏、肺脏、肾脏、肝脏的脏器质量(mg)/昆明小鼠体重(g)。After evaluating the learning ability of Kunming mice in each group by water maze, the Kunming mice were grabbed and weighed for 0 days, 14 days and 28 days, and then killed by decapitation. Liver, liver index, kidney index, heart index and lung index were calculated according to the formula. Calculation formula of liver index, kidney index, heart index and lung index: organ index of heart, lung, kidney and liver (mg/g) = organ mass of heart, lung, kidney and liver (mg) / body weight of Kunming mice (g).
2.9数据统计分析2.9 Statistical analysis of data
实验采用SPSS19.0软件分析本实验相关的数据(采用x±s表示)，多组间数据比较采用单因素方差分析。SPSS19.0 software was used in the experiment to analyze the data related to this experiment (represented by x±s), and one-way analysis of variance was used to compare the data among multiple groups.
3实验结果3 Experimental results
3.1中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力的影响3.1 The effect of traditional Chinese medicine composition on the learning ability of β-amyloid-induced Alzheimer's disease Kunming mice
实验结果表明，与不给药对照组比较，模型验证组昆明小鼠潜伏期明显延长(P＜0.05)，模拟手术组昆明小鼠潜伏期改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠潜伏期明显缩短(P＜0.05)，组合物低剂量组昆明小鼠潜伏期改变不明显(P＞0.05)。见表1。见图1。The experimental results showed that compared with the control group without drug administration, the incubation period of Kunming mice in the model validation group was significantly prolonged (P<0.05), while the incubation period of Kunming mice in the simulated operation group did not change significantly (P>0.05). The incubation period of Kunming mice in the intervention group, the high-dose composition group and the composition medium-dose group was significantly shortened (P<0.05), while the latent period of the Kunming mice in the low-dose composition group did not change significantly (P>0.05). See Table 1. see
表1中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠学习能力的影响
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.2中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠β-淀粉样蛋白前体蛋白的影响3.2 Effects of traditional Chinese medicine compositions on β-amyloid precursor protein in β-amyloid-induced Alzheimer's disease Kunming mice
实验结果表明，与不给药对照组比较，模型验证组昆明小鼠β-淀粉样蛋白前体蛋白含量明显增加(P＜0.05)，模拟手术组昆明小鼠β-淀粉样蛋白前体蛋白含量改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组病昆明小鼠β-淀粉样蛋白前体蛋白含量明显降低(P＜ 0.05)，组合物低剂量组昆明小鼠β-淀粉样蛋白前体蛋白含量改变不明显(P＞ 0.05)。见表2。见图2。The experimental results showed that, compared with the control group without administration, the content of β-amyloid precursor protein in Kunming mice in the model validation group was significantly increased (P<0.05), and the content of β-amyloid protein precursor protein in Kunming mice in the simulation operation group was significantly increased (P<0.05). The changes were not obvious (P>0.05); compared with the model validation group, the content of β-amyloid precursor protein in the Kunming mice in the western medicine intervention group, the high-dose composition group, and the composition medium-dose group was significantly decreased (P＜0.05) , the content of β-amyloid precursor protein in Kunming mice in the low-dose composition group did not change significantly (P>0.05). See Table 2. See Figure 2.
表2中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠β-淀粉样蛋白前体蛋白含量的影响
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.3中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠白介素-1β的影响3.3 The effect of traditional Chinese medicine composition on β-amyloid-induced Alzheimer's disease in Kunming mice with interleukin-1β
实验结果表明，与不给药对照组比较，模型验证组昆明小鼠白介素-1β含量明显增加(P＜0.05)，模拟手术组昆明小鼠白介素-1β含量改变不明显(P＞ 0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠白介素-1β含量明显降低(P＜0.05)，组合物低剂量组昆明小鼠白介素- 1β含量改变不明显(P＞0.05)。见表3。见图3。The experimental results showed that compared with the control group without administration, the content of interleukin-1β in Kunming mice in the model validation group increased significantly (P<0.05), while the content of interleukin-1β in Kunming mice in the simulated operation group did not change significantly (P>0.05); Compared with the model validation group, the content of interleukin-1β in Kunming mice in the western medicine intervention group, the high-dose composition group, and the medium-dose composition group was significantly decreased (P<0.05), while the content of interleukin-1β in Kunming mice in the low-dose composition group did not change significantly. (P>0.05). See Table 3. See Figure 3.
表3中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠白介素-1β含量的影响
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.4中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶的影响3.4 Effects of traditional Chinese medicine compositions on choline acetylase in Kunming mice with Alzheimer's disease induced by β-amyloid
结果表明，与不给药对照组比较，模型验证组昆明小鼠胆碱乙酰化酶平均光密度值明显减少(P＜0.05)，模拟手术组昆明小鼠胆碱乙酰化酶平均光密度值改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠胆碱乙酰化酶平均光密度值明显增加(P＜ 0.05)，组合物低剂量组昆明小鼠胆碱乙酰化酶平均光密度值改变不明显(P＞ 0.05)。见表4。见图4。The results showed that compared with the control group without drug administration, the average optical density of choline acetylase in Kunming mice in the model validation group was significantly decreased (P<0.05), and the average optical density of choline acetylase in Kunming mice in the simulated operation group changed. Compared with the model validation group, the average optical density of choline acetylase in Kunming mice in the western medicine intervention group, the high-dose composition group, and the composition medium-dose group increased significantly (P＜0.05). The average optical density of choline acetylase in Kunming mice in the low-dose group did not change significantly (P>0.05). See Table 4. See Figure 4.
表4中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶的影响
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.5中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶的影响3.5 Effects of traditional Chinese medicine compositions on acetylcholine metabolizing enzymes in Kunming mice with β-amyloid induced Alzheimer's disease
结果表明，与不给药对照组比较，模型验证组昆明小鼠乙酰胆碱代谢酶平均光密度值明显增加(P＜0.05)，模拟手术组昆明小鼠乙酰胆碱代谢酶平均光密度值改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠乙酰胆碱代谢酶平均光密度值明显减少(P＜ 0.05)，组合物低剂量组昆明小鼠乙酰胆碱代谢酶平均光密度值改变不明显(P ＞0.05)。见表5。见图5。The results showed that, compared with the control group without administration, the average optical density of acetylcholine metabolic enzyme in Kunming mice in the model validation group increased significantly (P<0.05), while the average optical density of acetylcholine metabolic enzyme in Kunming mice in the simulation operation group did not change significantly (P < 0.05). ＞0.05); compared with the model validation group, the average optical density of acetylcholine metabolizing enzyme in Kunming mice in the western medicine intervention group, the high-dose composition group, and the composition medium-dose group decreased significantly (P＜0.05), and the low-dose composition group Kunming small The average optical density of acetylcholine metabolizing enzymes in mice did not change significantly (P > 0.05). See Table 5. See Figure 5.
表5中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶的影响
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.6中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶基因的影响3.6 The effect of traditional Chinese medicine composition on β-amyloid-induced Alzheimer's disease choline acetylase gene in Kunming mice
结果表明，与不给药对照组比较，模型验证组昆明小鼠胆碱乙酰化酶基因表达量明显减少(P＜0.05)，模拟手术组昆明小鼠胆碱乙酰化酶基因表达量改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠胆碱乙酰化酶基因表达量明显增加(P＜0.05)，组合物低剂量组昆明小鼠胆碱乙酰化酶基因表达量改变不明显(P＞0.05)。见表6。见图6。The results showed that compared with the control group without drug administration, the expression of choline acetylase gene in Kunming mice in the model validation group was significantly decreased (P<0.05), and the expression of choline acetylase gene in Kunming mice in the simulated operation group did not change significantly. (P>0.05); compared with the model validation group, the expression of choline acetylase gene in Kunming mice was significantly increased in the western medicine intervention group, the high-dose composition group, and the medium-dose composition group (P<0.05), and the low-dose composition group significantly increased the expression of choline acetylase gene in Kunming mice. The expression of choline acetylase gene in Kunming mice in the group did not change significantly (P>0.05). See Table 6. See Figure 6.
表6中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠胆碱乙酰化酶基因的影响(
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.7中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶基因的影响3.7 The effect of traditional Chinese medicine composition on acetylcholine metabolizing enzyme gene of β-amyloid-induced Alzheimer's disease mice in Kunming mice
结果表明，与不给药对照组比较，模型验证组昆明小鼠乙酰胆碱代谢酶基因表达量明显增加(P＜0.05)，模拟手术组昆明小鼠乙酰胆碱代谢酶基因表达量改变不明显(P＞0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组昆明小鼠乙酰胆碱代谢酶基因表达量明显减少(P＜ 0.05)，组合物低剂量组昆明小鼠乙酰胆碱代谢酶基因表达量改变不明显(P＞ 0.05)。见表7。见图7。The results showed that compared with the control group without drug administration, the expression of acetylcholine metabolizing enzyme gene in Kunming mice in the model validation group increased significantly (P<0.05), while the expression level of acetylcholine metabolizing enzyme gene in Kunming mice in the simulated operation group did not change significantly (P>0.05). ); compared with the model validation group, the gene expression of acetylcholine metabolizing enzymes in Kunming mice in the western medicine intervention group, the high-dose composition group, and the medium-dose composition group decreased significantly (P＜0.05), and the low-dose composition group Kunming mice in the composition low-dose group metabolized acetylcholine significantly. There was no significant change in enzyme gene expression (P>0.05). See Table 7. See Figure 7.
表7中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠乙酰胆碱代谢酶基因的影响(
注：与不给药对照组比较：#P＜0.05，##P＞0.05；与模型验证组比较：*P＜ 0.05，**P＞0.05Note: Compared with the control group without administration: # P＜0.05, ## P＞0.05; compared with the model validation group: * P＜0.05, ** P＞0.05
3.8中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠心指数、肺指数的影响3.8 Effects of traditional Chinese medicine composition on cardiac index and lung index in Kunming mice with β-amyloid-induced Alzheimer's disease
结果表明，与不给药对照组比较，模型验证组昆明小鼠心指数、肺指数改变不明显(P＞0.05)，模拟手术组昆明小鼠心指数、肺指数改变不明显(P＞ 0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组、组合物低剂量组昆明小鼠心指数、肺指数改变不明显(P＞0.05)。见表8。见图8。The results showed that compared with the control group without drug administration, the heart index and lung index of Kunming mice in the model validation group did not change significantly (P>0.05), and the heart index and lung index of the Kunming mice in the simulated operation group did not change significantly (P>0.05). Compared with the model validation group, the cardiac index and lung index of Kunming mice in the western medicine intervention group, the composition high-dose group, the composition medium-dose group, and the composition low-dose group did not change significantly (P>0.05). See Table 8. See Figure 8.
表8中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠心指数、肺指数的影响(
注：与不给药对照组比较：#P＞0.05；与模型验证组比较：*P＞0.05Note: Compared with the control group without administration: # P＞0.05; compared with the model validation group: * P＞0.05
3.9中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠肾指数、肝指数的影响3.9 Effects of traditional Chinese medicine composition on kidney index and liver index of β-amyloid-induced Alzheimer's disease in Kunming mice
结果表明，与不给药对照组比较，模型验证组昆明小鼠肾指数、肝指数改变不明显(P＞0.05)，模拟手术组昆明小鼠肾指数、肝指数改变不明显(P＞ 0.05)；与模型验证组比较，西药干预组、组合物高剂量组、组合物中剂量组、组合物低剂量组昆明小鼠肾指数、肝指数改变不明显(P＞0.05)。见表9。见图9。The results showed that compared with the control group without administration, the kidney index and liver index of Kunming mice in the model validation group did not change significantly (P>0.05), and the kidney index and liver index of the Kunming mice in the simulated operation group did not change significantly (P>0.05). Compared with the model validation group, the kidney index and liver index of Kunming mice in the western medicine intervention group, the composition high-dose group, the composition medium-dose group, and the composition low-dose group did not change significantly (P>0.05). See Table 9. See Figure 9.
表9中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠肾指数、肝指数的影响(
注：与不给药对照组比较：#P＞0.05；与模型验证组比较：*P＞0.05Note: Compared with the control group without administration: # P＞0.05; compared with the model validation group: * P＞0.05
3.10中药组合物对β-淀粉样蛋白诱导阿尔茨海默病昆明小鼠体重的影响3.10 Effects of traditional Chinese medicine compositions on body weight of Kunming mice with β-amyloid-induced Alzheimer's disease
结果表明，与不给药对照组0天、14天、28天比较，模型验证组0天、14 天、28天昆明小鼠体重改变不明显(P＞0.05)，模拟手术组0天、14天、28 天昆明小鼠体重改变不明显(P＞0.05)；与模型验证组0天、14天、28天昆明小鼠体重比较，西药干预组、组合物高剂量组、组合物中剂量组、组合物低剂量组0天、14天、28天昆明小鼠体重改变不明显(P＞0.05)。见表10。见图 10。The results showed that, compared with the non-administration control group on
表10中药组合物对β-淀粉样蛋白诱导阿尔茨海默病清洁级昆明小鼠体重的影响(
注：与不给药对照组比较：#P＞0.05；与模型验证组比较：*P＞0.05。Note: Compared with the control group without administration: # P>0.05; compared with the model validation group: * P>0.05.
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