CN104800303A - Traditional Chinese medicine composition for treating Alzheimer's disease as well as preparation method and application of traditional Chinese medicine composition - Google Patents
Traditional Chinese medicine composition for treating Alzheimer's disease as well as preparation method and application of traditional Chinese medicine composition Download PDFInfo
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Abstract
The invention discloses traditional Chinese medicine composition for treating the Alzheimer's disease as well as a preparation method and an application of the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises milkvetch roots, Chinese angelica, red peony roots and prince's-feather fruits. Research indicates that the traditional Chinese medicine composition can improve the spatial learning ability and the spatial exploration ability of Kunming mice suffering from the Alzheimer's disease, increase visceral indexes of brains and spleens of the mice suffering from the Alzheimer's disease, reduce the permeability of Alzheimer's disease blood brain barriers, decrease Alzheimer's disease brain tissue hippocampal Abeta, IL-6 and IL-12 protein expression levels and have no obvious effect on weight of Alzheimer's disease models, namely, the Kunming mice. The results indicate that the traditional Chinese medicine composition is good in treatment effect on the Alzheimer's disease, so that the traditional Chinese medicine composition has the broad application prospect in the field of treatment of the Alzheimer's disease.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition and its production and use, particularly a kind of Chinese medicine composition being used for the treatment of Alzheimer and its preparation method and application, the invention belongs to Chinese medicine research technical field.
Background technology
Alzheimer is one of a kind of common Senile disease, and disturbance of intelligence and mental disorder thereof appear in the cerebral tissue showing as body, and this is a kind of comprehensive, multiple nervous system degenerative disease.The pathological manifestations of Alzheimer is the deposition that a large amount of amyloid plaques appears in cerebral tissue, the main component of speckle is amyloid-beta (A β), the precursor of A β is amyloid-beta precursor protein (APP), A β is a kind of 40-42 the amino acid whose peptide matters that APP is produced by α, β, gamma-secretase hydrolysis, mainly comprises A β
1-40with A β
1-42, wherein A β
1-40toxicity there is no A β
1-42greatly, based on this, experiment can adopt A β
1-42or A β
1-40alzheimer disease model is set up in cerebral tissue injection, carries out the experimentation to Alzheimer.Alzheimer disease model cerebral tissue Hippocampus A β horizontal abnormality, can observe the expression of Alzheimer disease model cerebral tissue Hippocampus A β based on this simultaneously.Alzheimer disease model behavioral indexes has more existing exception, so just need the Spatial learning ability and the space exploration ability thereof that detect Alzheimer disease model, judge the learning and memory ability of Alzheimer disease model, based on this, need the behavioral indexes detecting Alzheimer disease model.
Zlokovic proposes Alzheimer neural blood vessel hypothesis, think that blood brain barrier changes and cause multiple cascade reaction, the permeability changes of blood brain barrier affects cerebral tissue Hippocampus and causes (ZlokovicBV.Neurovascular mechanisms of Alzheimer ' s neurodegeneration [J] the .Trends Neurosci such as A β deposition to A β removing is abnormal, 2008, 28 (4): 202-208.), and the permeability of blood brain barrier can show (Wang Ping by the content detecting cerebral tissue EB, Lin Yang, Ge Feifei, Deng the impact [J] of .CRM197 on Cavia porcellus blood-brain barrier permeability. dissect scientific advance, 2008, 14 (4): 416-419.), based on this, the cerebral tissue EB content of Alzheimer disease model can be detected.The existing immunoreactive decline of Alzheimer multilist, the expression of a large amount of immune factors can be caused to increase, comprise the increase of the factors such as IL-6, IL-12, based on this can judge that the immune depression of Alzheimer reacts by measuring IL-6, IL-12 protein expression level (
richartz E,
stransky E,
batra A, et al.Decline ofimmune responsiveness:a pathogenetic factor In Alzheimer's disease? [J].
j Psychiatr res.2005Sep; 39 (5): 535-543.
swardfager W,
k,
rothenburg L, et al.Ameta-analysis of cytokines in Alzheimer's disease [J].
biol Psychiatry.2010Nov 15; 68 (10): 930-941.
lin HW,
levison SW.Context-dependent IL-6potentiation ofinterferon-gamma-induced IL-12secretion and CD40expression in murine microglia [J].
j Neurochem.2009Nov; 111 (3): 808-818.).
The Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra is one of composition of the ancient prescription BUYANG HUANWU TANG of motherland.BUYANG HUANWU TANG is one of ancient prescription of motherland's medical science, the present inventor's previous work points out that regulating action (Zhou Zhongguang can play to Alzheimer's Disease Rats serum caused by A β 1-40 and hippocampal tissue A β and cytokine content in BUYANG HUANWU TANG and the side of tearing open, Han Yusheng, Jiang Bo, etc. BUYANG HUANWU TANG and the side of tearing open are to A β
1-40the impact [J] of caused Alzheimer's Disease Rats serum and hippocampal tissue A β and cytokine content. Shanxi Medicine magazine, 2008,37 (2): 129-131.), on this basis, inventor improves BUYANG HUANWU TANG, namely a kind of Chinese medicine composition being used for the treatment of Alzheimer of the present invention is except the fractions Radix Astragali containing BUYANG HUANWU TANG, outside Radix Angelicae Sinensis and Radix Paeoniae Rubra, also have motherland's medicine Fructus Polygoni Orientalis, wherein Fructus Polygoni Orientalis has the effects such as antitumor, immunosuppressant, antioxidation, anti-hepatic fibrosis.
Experiment proves, compared to ancient prescription BUYANG HUANWU TANG, in Chinese medicine composition of the present invention, Radix Astragali dosage reduces about 2/3rds, but still can reach the therapeutic effect identical or close with BUYANG HUANWU TANG.Current Chinese medicine basic research is weaker, chemical composition complex in raw material of Chinese medicine medicine, and Effective Component of Chinese Medicine is indefinite, and Chinese medicine is multicomponent Mutiple Targets comprehensively plays a role, and therefore, flavour of a drug are more many more easily causes untoward reaction.Given this, the present inventor has simplified Chinese prescription, only selects the Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra and Fructus Polygoni Orientalis carry out prescription, and adopt A β 1-42 injection kunming mice hippocampus to prepare Alzheimer animal model, have carried out the research to control Alzheimer.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of Chinese medicine composition being used for the treatment of Alzheimer and its preparation method and application.
A kind of Chinese medicine composition being used for the treatment of Alzheimer of the present invention, is made up of each crude drug of following weight portion: Radix Astragali 30-50 weight portion, Radix Angelicae Sinensis 4-8 weight portion, Radix Paeoniae Rubra 3-7 weight portion and Fructus Polygoni Orientalis 15-25 weight portion.
In the present invention, preferably, described Chinese medicine composition is made up of each crude drug of following weight portion: the Radix Astragali 40 weight portion, Radix Angelicae Sinensis 6 weight portion, Radix Paeoniae Rubra 5 weight portion and Fructus Polygoni Orientalis 20 weight portion.
Further, the invention allows for a kind of Chinese medicine preparation being used for the treatment of Alzheimer suitable clinically, it is characterized in that adding adjuvant needed for preparations shaping by described Chinese medicine composition, make according to the conventional method of useful in preparing drug formulations.
In the present invention, preferably, described preparation is water decoction, capsule, pill, granule, tablet or oral liquid.
The preparation method of invention formulation belongs to conventional formulation method, and at this, there is no need to go into details.
Further, the invention allows for a kind of method preparing described Chinese medicine composition, it is characterized in that comprising the following steps:
(1) each crude drug is taken according to above-described weight portion;
(2) mixture of each crude drug is put into hub round-bottomed flask, add medical material gross weight 7-10 distilled water doubly, Glass rod stirs, and soaks 1.5-2.5h under enclosed environment, and heating decocts 1.5-2.5h, after cooling 10min.By multilamellar filtered through gauze medicinal material composition, until medicine does not have medicinal liquid to flow out, obtain first time filtrate;
(3) be put in hub round-bottomed flask by medicine residue again, add crude drug gross weight 7-10 times distilled water, the process repeating step (2) carries out second time filtration treatment, obtains second time filtrate, merges the filtrate of twice;
(4) filtrate obtains the extraction concentrated solution of Chinese medicine composition after bitubular steamer 70 DEG C of transpiring moistures, the extraction concentrated solution obtained continues dry 4-5d in 70 DEG C of electric heating constant-temperature blowing drying boxes, and the residue obtained is exactly the dry cream of described Chinese medicine composition.
Further, also comprise in above-described method and the dry cream of Chinese medicine composition is placed on crusher for crushing, grind, molecular sieve process repeatedly, obtain the powder of described Chinese medicine composition.
Preferably, in described method, the weight portion of described each crude drug is: the Radix Astragali 40 weight portion, Radix Angelicae Sinensis 6 weight portion, Radix Paeoniae Rubra 5 weight portion and Fructus Polygoni Orientalis 20 weight portion.
It is handling object that the present invention carries out with kunming mice, the micro sample adding appliance bilateral ventricles of the brain disposable injection 5 μ l condensed state A β under aseptic condition
1-42(80pmol μ l-1), preparation Alzheimer disease model.Adopt by Radix Astragali 40g, the Chinese medicine composition of Radix Angelicae Sinensis 6g, Radix Paeoniae Rubra 5g, Fructus Polygoni Orientalis 20g composition, the high, medium and low dosage 18.46gkg of setting Chinese medicine composition
-1d
-1, 9.23gkg
-1d
-1, 4.62gkg
-1d
-1three dosage groups carry out the experimentation to Alzheimer, be convenient to observe Chinese medicine composition to the impact of Alzheimer disease model kunming mice, the content of main detection and test comprises Spatial learning ability and the space exploration ability of Alzheimer kunming mice, brain organ index, the organ index of spleen, the permeability of blood brain barrier, cerebral tissue Hippocampus A β, IL-6, the body weight of IL-12 protein level and Alzheimer disease model kunming mice thereof, result shows, Chinese medicine composition of the present invention can improve the learning and memory function of Alzheimer disease model mice, reduce inflammation reaction, reduce the permeability of blood brain barrier, this Chinese medicine composition can play an important role in treatment of alzheimer by suppressing Hippocampus A β and other inflammatory factor albumen, aβ protein and IL-6 simultaneously, there is dependency in the change of IL-12 protein content.Below comprehensively show that the combined therapy effect of Chinese medicine composition of the present invention to Alzheimer is good.
Therefore, on this basis, the invention allows for the purposes of described Chinese medicine composition in preparation treatment Alzheimer disease drugs.
Accompanying drawing explanation
Fig. 1 is the impact of Chinese medicine composition of the present invention on Alzheimer mice orientation navigation ability;
Fig. 2 is the impact of Chinese medicine composition of the present invention on Alzheimer mice space exploration ability;
Fig. 3 is the impact of Chinese medicine composition of the present invention on Alzheimer mouse brain organ index;
Fig. 4 is the impact of Chinese medicine composition of the present invention on Alzheimer mouse spleen organ index;
Fig. 5 is the impact of Chinese medicine composition of the present invention on Alzheimer Mice brain tissues EB content;
Fig. 6 is the impact that Chinese medicine composition of the present invention is expressed Alzheimer mouse brain hippocampal tissue aβ protein;
Fig. 7 is the impact of Chinese medicine composition of the present invention on Alzheimer mouse brain hippocampal tissue IL-6 protein expression;
Fig. 8 is the impact of Chinese medicine composition of the present invention on Alzheimer mouse brain hippocampal tissue IL-12 protein expression;
Fig. 9 is the impact of Chinese medicine composition of the present invention on Alzheimer Mouse Weight.
Detailed description of the invention
Below by experiment, also the present invention will be further described in conjunction with the embodiments, it should be understood that these embodiments only for the object of illustration, never limit the scope of the invention.
Embodiment 1 one kinds is used for the treatment of the preparation of the Chinese medicine composition of Alzheimer
Chinese medicine composition of the present invention is made up of each crude drug of following weight: Radix Astragali 40g, Radix Angelicae Sinensis 6g, Radix Paeoniae Rubra 5g and Fructus Polygoni Orientalis 20g.
Embodiment 2 one kinds is used for the treatment of the preparation of the Chinese medicine composition of Alzheimer
Chinese medicine composition of the present invention is made up of each crude drug of following weight: Radix Astragali 35g, Radix Angelicae Sinensis 8g, Radix Paeoniae Rubra 4g and Fructus Polygoni Orientalis 24g.
Embodiment 3 one kinds is used for the treatment of the preparation of the Chinese medicine composition of Alzheimer
Chinese medicine composition of the present invention is made up of each crude drug of following weight: Radix Astragali 45g, Radix Angelicae Sinensis 5g, Radix Paeoniae Rubra 7g and Fructus Polygoni Orientalis 14g.
Embodiment 4 one kinds is used for the treatment of the preparation of the Chinese medicine composition (dry cream) of Alzheimer
The medical material that experiment uses comprises Radix Astragali 40g, Radix Angelicae Sinensis 6g, Radix Paeoniae Rubra 5g, Fructus Polygoni Orientalis 20g, and medical material Homogeneous phase mixing obtains 71g, according to same compound method preparation 10 this medical material secondary, obtains the medical material total amount of 710g.The mixture of 710g medical material is put into the hub round-bottomed flask of 20000ml, add 6000ml distilled water, Glass rod stirs, soak 2h under enclosed environment, heating decocts 2h, cooling 10min, by multilamellar filtered through gauze medicinal material composition, filtered through gauze residue, until medicine does not have medicinal liquid to flow out, obtains first time filtrate.Be put in hub round-bottomed flask by medicine residue, add 6000ml distilled water, the process above that repeats carries out second time filtration treatment, obtains second time filtrate, merges the filtrate of twice.
Filtrate obtains the extraction concentrated solution of Chinese medicine composition after bitubular steamer 70 DEG C of transpiring moistures, and the extraction concentrated solution obtained continues dry 4-5d in 70 DEG C of electric heating constant-temperature blowing drying boxes, and the residue obtained is exactly the dry cream of described Chinese medicine composition.
Experiment obtains the dry cream 267.1g of Chinese medicine composition, and Chinese medicine composition paste-forming rate is dry cream/Chinese medicinal material × 100%=37.62%.
Embodiment 5 one kinds is used for the treatment of the preparation of the Chinese medicine composition (powder) of Alzheimer
The dry cream of the Chinese medicine composition that Example 4 obtains, dry for Chinese medicine composition cream is placed on crusher for crushing, grind, molecular sieve process repeatedly, reduce the loss, obtain Chinese medicine composition dry powder 261.5g after crusher for crushing, the flour extraction of Chinese medicine composition is dry powder/Chinese medicinal material × 100%=36.83%.The actual medical material used is 710g, and the dry powder obtained is 261.5g, and therefore 1g Chinese medicine composition dry powder is equivalent to medicine original material 2.72g.
Take Chinese medicine composition dry powder 10g subpackage after electronic balance zeroing, sealing is placed on long-term in-80 DEG C of refrigerators preservation.
The purposes of embodiment 6 Chinese medicine composition of the present invention in treatment Alzheimer
1. material and instrument
1.1 material
54 male, 8 week ages, cleaning grade kunming mice, body weight 25 ± 3g, Experimental Animal Center Lee Baolong of Heilongjiang University of Chinese Medicine provides, certification of fitness: SCXK (black) 2013-004.Kunming mice is raised under Heilongjiang University of Chinese Medicine's Experimental Animal Center room temperature, normal wet, aseptic felicity condition, the free pickuping food of kunming mice and drinking water.Piracetam is bought in Hunan Dino Pharmaceutical Co, drug batch number: 130325.A β 1-42 is purchased from Sigma company.A β, IL-6, IL-12 enzyme linked immunological kit is bought and is built up Bioengineering Research Institute in Nanjing, lot number: 20140401.Distilled water is bought in literary composition scape distillation water factory of Harbin City.Radix Astragali lot number 131109, Radix Angelicae Sinensis lot number 131001, Radix Paeoniae Rubra lot number 121003, Fructus Polygoni Orientalis lot number 140922, is bought in the attached First Hospital of Heilongjiang University of Chinese Medicine by Chinese medicine study institute of Heilongjiang University of Chinese Medicine professor Zhou Zhongguang.Chinese medicine composition dry powder, according to the preparation of embodiment 5 method, when giving mouse stomach treatment, needs medical material dry composition to become to be equivalent to crude drug 18.46gkg
-1d
-1, 9.23gkg
-1d
-1, 4.62gkg
-1d
-1three dosage, and 37 DEG C are heated to Chinese medicine composition, are convenient to give mouse stomach.Other reagent are domestic analytical pure.
1.2 instrument
HMIAS high-definition color medical science picture and text analytical system, Wuhan thousand is shielded image technology company limited and is produced; RE-52A Rotary Evaporators, Shanghai Yarong Biochemical Instrument Plant produces; SIMF124 ice machine, SANYO GS company produces; CM1900 freezing microtome, Leica company produces; PLZOZ-S electronic balance, prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instrument Ltd. produces; Morris water maze, Northern Huaihe River Anhui Zheng Hua biological Instrument and equipments company limited produces; 6100 type RT-thunder Du microplate reader, RT company of the U.S. produces; TGL-16G desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces; Superclean bench, Suzhou Bo Laier cleaning equipment company limited produces; Alcohol meter, glass factory of Hejian City of Hebei province produces; 101-0AB type electric heating constant-temperature blowing drying box, Tianjin Stettlen Instrument Ltd. produces; Autoclave, Shanghai Medical Nuclear Instrument Factory produces.
2 methods
2.1 experiment groupings
Kunming mice divides matched group 9, model group 9, piracetam group 9, Chinese medicine composition high dose group (18.46gkg at random
-1d
-1) 9, dosage group (9.23gkg in Chinese medicine composition
-1d
-1) 9, Chinese medicine composition low dose group (4.62gkg
-1d
-1) 9, mice totally 54.
2.2 Alzheimer disease model copy
Observe the general state of kunming mice, capture kunming mice, dosage group and Chinese medicine composition low dose group mice in preference pattern group, piracetam group, Chinese medicine composition high dose group, Chinese medicine composition, 10% chloral hydrate is adopted to anaesthetize kunming mice, fixing mice, under aseptic condition, micro sample adding appliance is in the bilateral ventricles of the brain disposable injection 5 μ l condensed state A β of mice
1-42(80pmol μ l-1), syringe needle leaves 2min, and wrapping mice, allows mice fully have a rest, protect from infection.Matched group adopts the normal saline used the same method in the bilateral intracerebroventricular equivalent of mice simultaneously.
2.3 experimental administration
The dosage definition base of Radix Astragali 40g, Radix Angelicae Sinensis 6g, Radix Paeoniae Rubra 5g, Fructus Polygoni Orientalis 20g is: the drug dose of normal body standard body weight is 71g; by the ratio of people with the body surface area of mice; the drug dose of trying to achieve every 20g mice standard body weight is that 71g is multiplied by 0.0026; obtain the drug dose 0.1846g/20g of every 20g mice standard body weight; be converted into 9.23g/kg; this dosage is exactly the middle dosage of the mice medication carrying out testing, and the comparatively middle dosage of heavy dose doubles, and the comparatively middle dosage of low dose reduces by half.
Matched group, model group mice give the normal saline gavage of equivalent, and piracetam group gives piracetam 0.62gkg
-1d
-1gavage, Chinese medicine composition high dose group gives Chinese medicine composition 18.46gkg
-1d
-1in gavage, Chinese medicine composition, dosage group gives Chinese medicine composition 9.23gkg
-1d
-1gavage, Chinese medicine composition low dose group give Chinese medicine composition 4.62gkg
-1d
-1gavage, the gavage persistent period is 21d.
2.4 test position fix operational capabilities and space exploration ability
The capital equipment of Morris water maze test comprises: Morris water maze, computer camera system and software analysis system.Adopt Morris water maze instrument to detect each group of mice orientation navigation ability and space exploration ability, namely respectively organize learning capacity and the memory ability of mice.This Morris water maze instrument is circular pond, inside contains a transportable platform, platform has band, mice can be facilitated to stop, shooting instrument above pond is connected with computer, follows the tracks of at any time to the movement locus of mice, analyzes the corresponding experimental data of mice.Need the object of reference inside and outside holding chamber consistent when test, reduce extraneous interference.Morris water maze instrument depth of water 20cm, temperature controls in (23 ± 2) DEG C, puts prepared Chinese ink and form muddy black background in water, because mice is white, needs to manufacture black background, is convenient to carry out experiment.
Four quadrants are determined by shooting instrument.Wherein Morris water maze platform is put in the fourth quadrant of water maze, and other 3 quadrants are as the quadrant of test.Test the 1st, 2,3,4d is the training time, be trained for 60s at every turn, first, second and third quadrant mice head being put in respectively Morris water maze instrument towards outside when test carries out experimentation, records the swimming track of each mice and corresponding experimental data thereof.Test 5d test mice arrive the underwater platform position time be denoted as latency, weigh the orientation navigation ability of mice with this.Remove Morris water maze instrument platform when test 5d in addition, detect mice in 60s and find the swimming distance of platform as weighing mice space exploration ability, weigh the memory ability of mice with this.
2.5 measure organ index
After Morris water maze test experiments terminates 2h, superclean bench is placed ice platform, operate, rapid sacrificed by decapitation respectively organizes mice, to draw materials brain, the spleen organ of each group of mice, electronic balance accurately takes the Organ weight of mouse brain, spleen, carries out statistical analysis, calculates the organ index of mouse brain, spleen.
The computing formula of mice organs index: organ index (mgg
-1)=Organ weight (mg)/body weight (g)
2.6 measure cerebral tissue Azo-Blue (EB) content
Experiment is made into EB standard solution successively according to coubling dilution, and concentration is respectively 8,4,2,1,0.5,0.25 μ gml
-1, 6100 type RT-thunder Du microplate reader detect the absorbance (A) of 630nm.With EB concentration for abscissa, absorbance (A) is vertical coordinate, draws the standard curve of EB content, asks EB content standard curvilinear equation.
After Morris water maze test experiments terminates 2h, the tail vein injection 2%EB solution of each group mice, after obvious blueness appears in the whole skin observing mice at any time, shows the success of 2%EB injection of solution.After the success of 2%EB injection of solution, mice chloral hydrate is anaesthetized, mice fixed by cord, adopt aseptic transfusion device to the left ventricle of mice perfusion 100ml normal saline, ice platform dissected rapidly, formamide solution soaks, lucifuge is hatched, homogenate, centrifugal 10min.Use 6100 type RT-thunder Du microplate reader of RT company of the U.S., select 630nm place to measure supernatant absorbance (A).EB concentration (μ gml is obtained according to EB standard curve
-1), EB content (the μ gg of mice is obtained in the quality by Mice brain tissues
-1), heavy (the μ gg of EB content EB concentration/cutaneous horn
-1) ratio represent.
2.7 measure Hippocampus of Mice A β, IL-6 and IL-12 protein content
After Morris water maze test experiments terminates 2h, each group of mice sacrificed by decapitation on superclean bench, remove cerebral tissue skin, open cranium, take out complete mouse brain tissue and be placed on ice platform, remove brain stem and cerebellum, get rapidly the hippocampal tissue of each group of mice, homogenate Hippocampus of Mice, 4 DEG C of refrigerators leave standstill, 5000rpmmin
-1centrifugal 10min, draws hippocampal tissue supernatant, subpackage ,-20 DEG C of preservations.Operate by enzyme linked immunological kit description, use 6100 type RT-thunder Du microplate reader 450nm wavelength places to measure each hole absorbance (A), try to achieve the content of mouse brain hippocampal tissue A β, IL-6 and IL-12 albumen.
2.8 measure body weight
Experimental session measures Mouse Weight every day, and before experiment terminates, last mensuration kunming mice body weight, with the Mouse Weight finally surveyed for Exemplary statistical data, calculates the weight differences respectively organizing mice.
2.9 statistical analysis
Adopt SPSS19.0 software to carry out statistical procedures, experimental data adopts
represent, compare between many groups and adopt one factor analysis of variance experimental data.P<0.05 thinks that difference has statistical significance.
3 results
3.1 Chinese medicine compositions are on the impact of Alzheimer mice orientation navigation ability
Mice orientation navigation ability represented with incubation period.Result shows, compares with matched group, and model group mice obviously extends (P < 0.05) incubation period; Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group mice obviously shortens (P < 0.05) (see table 1, Fig. 1) incubation period.
Table 1 Chinese medicine composition is on the impact of Alzheimer mice orientation navigation ability
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.2 Chinese medicine compositions are on the impact of Alzheimer mice space exploration ability
Mice space exploration ability swimming distance represents.Result shows, compares with matched group, and model group mice swimming distance obviously increases (P < 0.05); Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group mice swimming distance obviously reduces (P < 0.05) (see table 2, Fig. 2).
Table 2 Chinese medicine composition is on the impact of Alzheimer mice space exploration ability
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.3 Chinese medicine compositions are on the impact of Alzheimer mouse brain organ index
Analyzed from table 3, compare with matched group, model group Alzheimer mouse brain organ index obviously reduces (P < 0.05), compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group Alzheimer mouse brain organ index obviously raises (P < 0.05) (see table 3, Fig. 3).
Table 3 Chinese medicine composition is on the impact of Alzheimer mouse brain organ index
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.4 Chinese medicine compositions are on the impact of Alzheimer mouse spleen organ index
Analyzed from table 4, compare with matched group, the organ index of model group Alzheimer mouse spleen obviously reduces (P < 0.05), compare with model group, the organ index of piracetam group, Chinese medicine composition high, medium and low dosage group mouse spleen obviously raises (P < 0.05) (see table 4, Fig. 4).
Table 4 Chinese medicine composition is on the impact of Alzheimer mouse spleen organ index
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.5 Chinese medicine compositions are on the impact of Alzheimer Mice brain tissues EB content
Analyzed from table 5, compare with matched group, model group Alzheimer Mice brain tissues EB content obviously raises (P < 0.05); Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group Alzheimer Mice brain tissues EB content obviously reduces (P < 0.05) (see table 5, Fig. 5).
Table 5 Chinese medicine composition is on the impact of Alzheimer Mice brain tissues EB content
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
The impact that 3.6 Chinese medicine compositions are expressed Alzheimer mouse brain hippocampal tissue aβ protein
Analyzed from table 6, compare with matched group, model group mice Alzheimer cerebral hippocampal organizes aβ protein content obviously to raise (P < 0.05); Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group cerebral hippocampal organizes aβ protein content obviously to reduce (P < 0.05) (see table 6, Fig. 6).
The impact that table 6 Chinese medicine composition is expressed Alzheimer mouse brain hippocampal tissue aβ protein
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.7 Chinese medicine compositions are on the impact of Alzheimer mouse brain hippocampal tissue IL-6 protein expression
From table 7, compare with matched group, model group Alzheimer Hippocampus of Mice IL-6 protein content obviously raises (P < 0.05); Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group Alzheimer Hippocampus of Mice IL-6 protein content obviously reduces (P < 0.05) (see table 7, Fig. 7).
Table 7 Chinese medicine composition is on the impact of Alzheimer mouse brain hippocampal tissue IL-6 protein expression
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.8 Chinese medicine compositions are on the impact of Alzheimer mouse brain hippocampal tissue IL-12 protein expression
From table 8, compare with matched group, model group Alzheimer Hippocampus of Mice IL-12 protein content obviously raises (P < 0.05); Compare with model group, piracetam group, Chinese medicine composition high, medium and low dosage group Alzheimer Hippocampus of Mice IL-12 protein content obviously reduces (P < 0.05) (see table 8, Fig. 8).
Table 8 Chinese medicine composition is on the impact of Alzheimer mouse brain hippocampal tissue IL-12 protein expression
Note: compare with matched group:
1)p < 0.05; Compare with model group:
2)p < 0.05
3.9 Chinese medicine compositions are on the impact of Mouse Weight
Result shows, compares with matched group, and the body weight of model group mice changes not obvious (P > 0.05); Compare with model group, the Mouse Weight of piracetam group, Chinese medicine composition high, medium and low dosage group changes not obvious (P > 0.05) (see table 9, Fig. 9).
Table 9 Chinese medicine composition is on the impact of Alzheimer Mouse Weight
Note: compare with matched group:
1)p > 0.05; Compare with model group:
2)p > 0.05
4 conclusions
The ethological testing result display of this zoopery, the ability of learning and memory of model group mice obviously declines, model stability, is suitable for carrying out experimentation.The ability of learning and memory of Chinese medicine composition high, medium and low dosage group mice obviously improves, and the high, medium and low dosage of prompting Chinese medicine composition obviously can improve the ability of learning and memory of Alzheimer disease model mice.More than illustrate that Radix Astragali 40g, Radix Angelicae Sinensis 6g, Radix Paeoniae Rubra 5g, Fructus Polygoni Orientalis 20g Chinese medicine composition can improve Alzheimer kunming mice Spatial learning ability and space exploration ability.
Measuring mouse spleen, brain organ index display, the mass fraction of model group mouse brain and spleen is abnormal, mouse brain and splenic injury heavier, body brain function weakens, and anti-infection ability weakens.The high, medium and low dosage group of Chinese medicine composition can improve the brain of mice and the mass fraction of spleen, the anti-infection ability of enhancing body, the prompting Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis Chinese medicine composition recover the partial function of spleen, brain, have certain restitution to the effect of Alzheimer disease model mouse corrosion disease and brain function thereof.More than illustrate that motherland's medicine Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis crude drug composition can have certain protective effect to Alzheimer kunming mice cerebral tissue and spleen.
The EB content of measuring cerebral tissue, compares with matched group, and model group Mice brain tissues EB content obviously raises (P < 0.05), illustrates that the permeability of Blood-Brain Barrier increases, has increased the weight of exotic matter and entered cerebral tissue; Compare with model group, Chinese medicine composition high, medium and low dosage group Mice brain tissues EB content obviously reduces (P < 0.05), illustrate that the Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis Chinese medicine composition obviously improve the permeability of Blood-Brain Barrier, the change of cerebral tissue permeability changes consistent with the organ index of brain, spleen, with the increase of certain blood-brain barrier permeability while prompting brain tissue inflammation significant reaction.More than illustrate that motherland's medicine Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis crude drug composition obviously can improve the permeability of Alzheimer kunming mice blood brain barrier.
Test the content being measured aβ protein by enzyme-linked immunoassay method, result shows, the key link composition aβ protein content of the hippocampal tissue onset of Alzheimer disease of model mice obviously raises.The Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, the high, medium and low dosage of Fructus Polygoni Orientalis Chinese medicine composition improve developing of Alzheimer by affecting aβ protein.Below the Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis Chinese medicine composition high, medium and low dosage treatment Alzheimer is comprehensively pointed out to have obvious effect, and play the therapeutical effect to Alzheimer by A β.
Experiment measures the content of IL-6, IL-12 albumen by enzyme-linked immunoassay method, result shows, compare with matched group, model group Hippocampus of Mice IL-6, IL-12 protein content obviously raises (P < 0.05), illustrate that model group inflammatory reaction is obvious, a large amount of inflammatory factors take part in developing of Alzheimer, compare with model group, Chinese medicine composition object height, in, low dose group hippocampal tissue IL-6, IL-12 protein content obviously reduces (P < 0.05), the Radix Astragali is described, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis Chinese medicine composition obviously improves the inflammatory reaction of Hippocampus of Mice, IL-6, the trend of IL-12 albumen and aβ protein is close, illustrate that these factors are important correlation factors that Alzheimer is evaluated, also illustrate at Alzheimer Hippocampus of Mice key link factors A β albumen and immune inflammatory factor IL-6 simultaneously, there is certain dependency in IL-12 albumen.
After experiment terminates, compare with matched group, model group kunming mice body weight changes not obvious (P > 0.05); Compare with model group, Chinese medicine composition high, medium and low dosage group kunming mice Alzheimer body weight changes also not obvious (P > 0.05), the body weight of kunming mice can not be changed while the Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Polygoni Orientalis traditional Chinese medicine composition for treating Alzheimer are described, show that the Radix Astragali, Radix Angelicae Sinensis, Radix Paeoniae Rubra, the side effect of Fructus Polygoni Orientalis mixture are less, be applicable to carrying out the treatment for Alzheimer.
In sum, Chinese medicine composition of the present invention can improve the learning and memory function of Alzheimer disease model mice, reduce inflammation reaction, reduce the permeability of blood brain barrier, Chinese medicine composition can play an important role in treatment of alzheimer by suppressing Hippocampus A β and other inflammatory factor albumen, simultaneously aβ protein and IL-6, IL-12 protein content change and there is dependency, and concrete mechanism needs further experimentation.Below comprehensively show that the combined therapy effect of Chinese medicine composition of the present invention to Alzheimer is good.
The foregoing is only the preferred embodiments of the present invention, is only illustrative for the purpose of the present invention, and nonrestrictive; Those of ordinary skill in the art understand, and can carry out many changes in the spirit and scope that the claims in the present invention limit to it, amendment, and even equivalence is changed, but all will fall within the scope of protection of the present invention.
Claims (8)
1. be used for the treatment of a Chinese medicine composition for Alzheimer, it is characterized in that being made up of each crude drug of following weight portion: Radix Astragali 30-50 weight portion, Radix Angelicae Sinensis 4-8 weight portion, Radix Paeoniae Rubra 3-7 weight portion and Fructus Polygoni Orientalis 15-25 weight portion.
2. Chinese medicine composition as claimed in claim 1, is characterized in that being made up of each crude drug of following weight portion: the Radix Astragali 40 weight portion, Radix Angelicae Sinensis 6 weight portion, Radix Paeoniae Rubra 5 weight portion and Fructus Polygoni Orientalis 20 weight portion.
3. the Chinese medicine preparation being used for the treatment of Alzheimer suitable clinically, is characterized in that adding adjuvant needed for preparations shaping by the Chinese medicine composition described in claim 1 or 2, makes according to the conventional method of useful in preparing drug formulations.
4. Chinese medicine preparation as claimed in claim 3, is characterized in that described preparation is water decoction, capsule, pill, granule, tablet or oral liquid.
5. prepare a method for Chinese medicine composition according to claim 1, it is characterized in that comprising the following steps:
(1) each crude drug is taken according to weight portion according to claim 1;
(2) mixture of each crude drug is put into hub round-bottomed flask, add medical material gross weight 7-10 distilled water doubly, Glass rod stirs, 1.5-2.5h is soaked under enclosed environment, heating decocts 1.5-2.5h, after cooling 10min, by multilamellar filtered through gauze medicinal material composition, until medicine does not have medicinal liquid to flow out, obtain first time filtrate;
(3) be put in hub round-bottomed flask by medicine residue again, add crude drug gross weight 7-10 times distilled water, the process repeating step (2) carries out second time filtration treatment, obtains second time filtrate, merges the filtrate of twice;
(4) filtrate obtains the extraction concentrated solution of Chinese medicine composition after bitubular steamer 70 DEG C of transpiring moistures, the extraction concentrated solution obtained continues dry 4-5d in 70 DEG C of electric heating constant-temperature blowing drying boxes, and the residue obtained is exactly the dry cream of described Chinese medicine composition.
6. method as claimed in claim 5, characterized by further comprising and the dry cream of Chinese medicine composition is placed on crusher for crushing, grind, molecular sieve process repeatedly, obtain the powder of described Chinese medicine composition.
7. method as claimed in claim 5, is characterized in that the weight portion of described each crude drug is: the Radix Astragali 40 weight portion, Radix Angelicae Sinensis 6 weight portion, Radix Paeoniae Rubra 5 weight portion and Fructus Polygoni Orientalis 20 weight portion.
8. the purposes of Chinese medicine composition as claimed in claim 1 or 2 in preparation treatment Alzheimer disease drugs.
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| CN109999179A (en) * | 2019-05-08 | 2019-07-12 | 山东省分析测试中心 | Low dosage interleukin-22 is used to prepare the application in treatment Alzheimer disease drugs |
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| CN105998316A (en) * | 2016-05-23 | 2016-10-12 | 齐齐哈尔医学院 | Traditional Chinese medicine composition for treating alzheimer's disease, and preparation method and application thereof |
| CN105998316B (en) * | 2016-05-23 | 2019-12-03 | 齐齐哈尔医学院 | A kind of Chinese medicine composition for treating senile dementia and its specific preparation method and related application |
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