CN116392477A - 小白菊内酯在制备治疗肺动脉高压的药物中的应用 - Google Patents
小白菊内酯在制备治疗肺动脉高压的药物中的应用 Download PDFInfo
- Publication number
- CN116392477A CN116392477A CN202310330148.0A CN202310330148A CN116392477A CN 116392477 A CN116392477 A CN 116392477A CN 202310330148 A CN202310330148 A CN 202310330148A CN 116392477 A CN116392477 A CN 116392477A
- Authority
- CN
- China
- Prior art keywords
- parthenolide
- arterial hypertension
- pulmonary arterial
- medicine
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- BUQLXKSONWUQAC-UHFFFAOYSA-N Parthenolide Natural products CC1C2OC(=O)C(=C)C2CCC(=C/CCC1(C)O)C BUQLXKSONWUQAC-UHFFFAOYSA-N 0.000 title claims abstract description 56
- KTEXNACQROZXEV-PVLRGYAZSA-N parthenolide Chemical compound C1CC(/C)=C/CC[C@@]2(C)O[C@@H]2[C@H]2OC(=O)C(=C)[C@@H]21 KTEXNACQROZXEV-PVLRGYAZSA-N 0.000 title claims abstract description 56
- 229940069510 parthenolide Drugs 0.000 title claims abstract description 56
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title description 2
- 229940079593 drug Drugs 0.000 claims abstract description 9
- 206010021143 Hypoxia Diseases 0.000 claims description 34
- 230000007954 hypoxia Effects 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 12
- 210000001147 pulmonary artery Anatomy 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000004872 arterial blood pressure Effects 0.000 claims description 5
- 208000032594 Vascular Remodeling Diseases 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 238000011160 research Methods 0.000 abstract description 3
- 208000002815 pulmonary hypertension Diseases 0.000 description 20
- 230000001146 hypoxic effect Effects 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- 238000011552 rat model Methods 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- MAOBEYNUXMAMLT-VAOFZXAKSA-N 1-[(2s,4s,5r)-2-ethynyl-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@@]1(C#C)N1C(=O)NC(=O)C=C1 MAOBEYNUXMAMLT-VAOFZXAKSA-N 0.000 description 2
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 210000005241 right ventricle Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010970 Cor pulmonale chronic Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000010180 Endothelin receptor Human genes 0.000 description 1
- 108050001739 Endothelin receptor Proteins 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 102000002177 Hypoxia-inducible factor-1 alpha Human genes 0.000 description 1
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000019040 Nuclear Antigens Human genes 0.000 description 1
- 108010051791 Nuclear Antigens Proteins 0.000 description 1
- 241000244269 Peucedanum Species 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 206010039163 Right ventricular failure Diseases 0.000 description 1
- 208000000924 Right ventricular hypertrophy Diseases 0.000 description 1
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 208000026636 chronic pulmonary heart disease Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000022082 negative regulation of vasoconstriction Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229950003647 semaxanib Drugs 0.000 description 1
- 229930009674 sesquiterpene lactone Natural products 0.000 description 1
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000022379 skeletal muscle tissue development Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000000596 ventricular septum Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及生物医药技术领域,具体涉及小白菊内酯在制备治疗肺动脉高压的药物中的应用。本发明开发了小白菊内酯新的用途,使小白菊内酯得到更好的应用;为肺动脉高压治疗提供新的药物研究方向,具有很好的应用前景。
Description
技术领域
本发明涉及生物医药技术领域,具体涉及小白菊内酯在制备治疗肺动脉高压的药物中的应用。
背景技术
肺动脉高压(PH)是一组临床特征为肺循环压力异常升高,最终导致右心室衰竭和死亡的疾病。肺动脉高压分为5类,其中低氧性肺动脉高压为我国最常见的肺动脉高压类型。慢性阻塞性肺疾病(COPD)为临床常见病、多发病,可引起低氧性肺动脉高压和慢性肺源性心脏病,给我国带来了巨大的经济和劳动力损失。
目前对于低氧肺动脉高压的治疗主要以血管舒张剂为主,治疗PH的药物主要包括前列环素类药物、内皮素受体阻滞剂、磷酸二酯酶抑制剂-5等。虽然对早期患者可改善其症状,但不能逆转其病程,疗效有限,且价格昂贵,对于病人预后生存可能并无改善。因此寻找新的药物以延缓肺动脉高压进展成为十分重要的研究课题。
小白菊内酯(PTL)是从短舌匹菊中发现的倍半萜内酯,其分子式为C15H20O3。小白菊内酯主要来源于传统药用植物——小白菊,具有抗炎、抗纤维化、抗肿瘤以及调节氧化还原和表观遗传活性等特性。新近研究表明,小白菊内酯抑制缺氧诱导因子-1α(HIF-1α)信号传导、降低血管生成相关的蛋白水平、调节细胞周期从而抑制胸主动脉平滑肌细胞增殖,同时还可调控环氧化酶2(COX-2)抑制血管收缩。这些研究都提示小白菊内酯可能成为低氧性肺动脉高压潜在治疗药物之一。
发明内容
本发明的目的是为了克服现有技术存在的缺点和不足,而提供一种小白菊内酯在制备治疗肺动脉高压的药物中的应用。为实现上述目的,本发明基于“肺动脉高压无特效靶向药及现有药物价格昂贵”的临床现状,探索小白菊内酯是否可以成为治疗肺动脉高压的潜在药物,以及其发挥作用的具体机制及靶点。
本发明的第一个方面是提供小白菊内酯在制备治疗肺动脉高压的药物中的应用。
优选的,所述肺动脉高压为低氧及低氧联合司马沙尼(Sugen5416)诱导形成的肺动脉高压。
优选的,所述药物用于改善肺动脉压力。
优选的,所述药物用于改善血管重塑。
本发明的第二个方面是提供一种用于治疗肺动脉高压的药物组合物,其含有如上所述的小白菊内酯或其药学上可接受的盐。
如本文所用,“药学上可接受的”的成分是适用于人和/或哺乳动物而无过度不良副反应(如毒性)的,即具有合理的效益/风险比的物质。合适的盐是本领域普通技术人员所熟知的。
优选的,所述小白菊内酯或其药学上可接受的盐作为其中一种药用活性成分。
优选的,药物的给药形式包括胶囊剂、片剂、粉剂、粒剂、糖浆或类似剂型形式的口服给药,或通过注射、软膏、栓剂或类似剂型的非口服给药。这些药物制剂可通过使用本领域熟知的辅助剂,如粘合剂,赋形剂,稳定剂,崩解剂,矫味剂,润滑剂等等以普通方法生成,也可以制备为控释给药剂型、缓释给药剂型、各种微粒给药系统。
优选的,药物的给药形式为胶囊剂、片剂、粉剂、粒剂、糖浆或类似剂型形式的口服给药,所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量1-1000mg。虽然剂量随症状和病人的年龄,疾病或失调的性质及严重性和给药的途径和方式而变,但对成年病人口服给药的情况来说,小白菊内酯或其药学上可接受的盐正常给药为每天总剂量1至1000mg,可以为单剂量或者为分剂量形式给药;例如每日一次、二次或三次。
优选的,所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量20-800mg。
优选的,所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量50-600mg。
本发明的有益效果如下:本发明开发了小白菊内酯新的用途,使小白菊内酯得到更好的应用;为肺动脉高压治疗提供新的药物研究方向,具有很好的应用前景。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动性的前提下,根据这些附图获得其他的附图仍属于本发明的范畴。
图1为小白菊内酯的天然来源和化学结构式;
图2为小白菊内酯缓解低氧性肺动脉高压大鼠模型的肺动脉压力;
图3为小白菊内酯缓解低氧性肺动脉高压大鼠模型右心室肥厚;
图4为小白菊内酯缓解低氧性肺动脉高压大鼠模型血管重塑;
图5为小白菊内酯缓解低氧性肺动脉高压大鼠模型肺动脉平滑肌细胞的增殖;
图6为小白菊内酯抑制低氧下大鼠肺动脉平滑肌细胞(rPASMC)的增殖;
图7为小白菊内酯抑制低氧下大鼠肺动脉平滑肌细胞(rPASMC)的迁移;
图2-7中,*:P<0.05;**:P<0.01;***:P<0.001;****:P<0.0001。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚,下面将结合附图对本发明作进一步地详细描述。
如图1所示为小白菊内酯的天然来源和化学结构式。
本发明实施例通过以下实验对小白菊内酯在制备治疗肺动脉高压的药物中应用的可行性进行验证。
实施例1、低氧肺动脉高压(HPH)大鼠模型的建立
将30只体重为170-200g健康雄性SD野生大鼠随机分为3组,每组10只,分别为:常氧组(Nx)、低氧组(Hx)、低氧+小白菊内酯干预组(P30)。除常氧组暴露于空气外,其余两组每天低氧造模24h(低氧舱内氧气浓度为10%)。常氧组和低氧组小鼠接受相同的光照条件和饮食供给。对于小白菊内酯给药组老鼠,隔天根据体重腹腔注射相应量(30mg/kg),对照组腹腔注射对应量的生理盐水,持续3周。3周后,将所有大鼠麻醉并进行有创血流动力学测量,然后收集大鼠肺等组织进行进一步研究。
实施例2、小白菊内酯对HPH模型大鼠肺动脉压力的影响
实施例1中的低氧性肺动脉高压(HPH)大鼠模型造模3周后,通过血流动力学及右心室重构评估发现,小白菊内酯可明显降低低氧性肺动脉高压大鼠模型的平均肺动脉收缩压(mPAP)(图2AC),而平均颈动脉压力(mCAP)无明显差异(图2BD),同时发现小白菊内酯可降低低氧性肺动脉高压大鼠右心室/(左心室+室间隔)(RV/ (LV +S))比率(图3A)。上述结果证明了小白菊内酯可以缓解低氧性肺动脉高压大鼠模型的肺动脉压力。
实施例3、小白菊内酯对HPH模型大鼠肺血管组织形态学的变化的影响
实施例1中的低氧性肺动脉高压(HPH)大鼠模型造模3周后,通过对肺组织切片进行苏木精/伊红(H&E)染色、马松(MASSON)染色等病理研究发现,小白菊内酯显着减弱了低氧性肺动脉高压模型大鼠的肺动脉肌化(图4AB),逆转了肺动脉高压模型大小鼠的肺动脉周围胶原蛋白过度沉积(图4AC)。上述结果证明了小白菊内酯可以缓解肺动脉高压大鼠模型的血管重塑。
实施例4、小白菊内酯对HPH模型大鼠肺组织中细胞增殖核抗原(PCNA)蛋白表达的影响
实施例1中的低氧性肺动脉高压大鼠模型造模3周后,通过将大鼠肺组织制成匀浆,提取总蛋白,蛋白印迹法(Western Blot)检测发现造模大鼠肺组织中PCNA蛋白表达水平显著上升,而小白菊内酯可显著降低其表达水平(图5AB)。
实施例5、细胞模型的建立
取3-5代的大鼠肺动脉平滑肌细胞(rPASMCs)进行实验。实验分为3组:常氧对照组(Nx)、低氧造模组(Hx)、低氧+小白菊内酯(4μM/ml)给药组。低氧造模组将贴壁细胞放置在37℃恒温低氧培养箱中(保持O2浓度10%,CO2浓度5%)造模24小时。常氧对照组选取同样密度的贴壁细胞在37℃恒温培养箱(O2浓度21%、CO2浓度5%)培养24小时。24小时后,进一步进行细胞实验。
实施例6、小白菊内酯对低氧下细胞增殖的影响
实施例5细胞造模后,通过提取细胞总蛋白,Western Blot法检测发现低氧下细胞中PCNA增殖指标明显上调,而小白菊内酯可显著降低其表达水平(图6AC);通过5-2’乙炔基-脱氧尿苷(EDU)掺入细胞增殖实验发现小白菊内酯显著抑制低氧下细胞的增殖(图6BD)。
实施例7、小白菊内酯对低氧下细胞迁移的影响
实施例5细胞造模后,通过小室细胞侵袭实验(Transwell)检测发现小白菊内酯还可显著抑制低氧下细胞的迁移(图7AB)。
以上所揭露的仅为本发明较佳实施例而已,当然不能以此来限定本发明之权利范围,因此依本发明权利要求所作的等同变化,仍属本发明所涵盖的范围。
Claims (10)
1.小白菊内酯在制备治疗肺动脉高压的药物中的应用。
2.根据权利要求1所述的应用,其特征在于:所述肺动脉高压为低氧及低氧联合Sugen5416诱导形成的肺动脉高压。
3.根据权利要求1或2所述的应用,其特征在于:所述药物用于改善肺动脉压力。
4.根据权利要求1或2所述的应用,其特征在于:所述药物用于改善血管重塑。
5.一种用于治疗肺动脉高压的药物组合物,其含有如权利要求1所述的小白菊内酯或其药学上可接受的盐。
6.根据权利要求5所述的药物组合物,其特征在于:所述小白菊内酯或其药学上可接受的盐作为其中一种药用活性成分。
7.根据权利要求5或6所述的药物组合物,其特征在于:药物的给药形式包括胶囊剂、片剂、粉剂、粒剂、糖浆或类似剂型形式的口服给药,或通过注射、软膏、栓剂或类似剂型的非口服给药。
8.根据权利要求7所述的药物组合物,其特征在于:药物的给药形式为胶囊剂、片剂、粉剂、粒剂、糖浆或类似剂型形式的口服给药,所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量1-1000mg。
9.根据权利要求8所述的药物组合物,其特征在于:所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量20-800mg。
10.根据权利要求8所述的药物组合物,其特征在于:所述药物中小白菊内酯或其药学上可接受的盐正常给药为每天总剂量50-600mg。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310330148.0A CN116392477A (zh) | 2023-03-30 | 2023-03-30 | 小白菊内酯在制备治疗肺动脉高压的药物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310330148.0A CN116392477A (zh) | 2023-03-30 | 2023-03-30 | 小白菊内酯在制备治疗肺动脉高压的药物中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116392477A true CN116392477A (zh) | 2023-07-07 |
Family
ID=87017212
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310330148.0A Pending CN116392477A (zh) | 2023-03-30 | 2023-03-30 | 小白菊内酯在制备治疗肺动脉高压的药物中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116392477A (zh) |
-
2023
- 2023-03-30 CN CN202310330148.0A patent/CN116392477A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cuthbert | Effect on airways resistance of prostaglandin E1 given by aerosol to healthy and asthmatic volunteers | |
CN107427502A (zh) | 使用川地匹坦的治疗方法 | |
CN110248646A (zh) | 包含吡非尼酮的缓释组合物用于治疗和逆转人脂肪性肝炎(nafld/nash)的药物用途 | |
TW201345539A (zh) | 牛樟芝用於治療疾病的方法 | |
Minor et al. | Prolonged methylene blue infusion in refractory septic shock: a case report | |
Yang et al. | The protective effect of rhBNP on postresuscitation myocardial dysfunction in a rat cardiac arrest model | |
WO2022073416A1 (zh) | 微囊藻毒素-rr在用于制备预防或治疗肾纤维化疾病的药物中的应用 | |
Catalano et al. | Famotidine-associated delirium: A series of six cases | |
CN116392477A (zh) | 小白菊内酯在制备治疗肺动脉高压的药物中的应用 | |
EP4342475A1 (en) | Composition for treatment of covid-19 comprising taurodeoxycholic acid or pharmaceutically acceptable salt thereof as active ingredient | |
US20220332796A1 (en) | Fused polypeptide with multifunctional activities and use thereof | |
CN113648380A (zh) | 一种治疗糖尿病的组合物 | |
CN116392462A (zh) | 毛兰素在制备治疗肺动脉高压的药物中的应用 | |
CN111000983A (zh) | 一种新的重组人白细胞介素-1受体拮抗剂的药用用途 | |
JPH02209812A (ja) | 乾癬治療用医薬組成物 | |
CN116617239A (zh) | 淫羊藿次苷ii在治疗肺动脉高压疾病中的应用 | |
Burns et al. | Effect of naftidrofuryl on the metabolic response to surgery. | |
CN1299676C (zh) | 一种抗缺氧药物组合物 | |
CN104688939B (zh) | 治疗慢性阻塞性肺病的中药组合物及其制备方法 | |
US20190381034A1 (en) | Pharmaceutical composition and method for acute on chronic liver failure and related liver diseases | |
CN116251098B (zh) | 去氢骆驼蓬碱在制备治疗和/或预防肺动脉高压的药物中的用途 | |
CN108379557A (zh) | 使用白介素因子-37治疗特发性肺纤维化 | |
CN108272854A (zh) | 一种用于防治化疗性口腔炎症的药物及其制备方法 | |
CN102631355B (zh) | 一种含有阿司匹林的药物组合物及用途 | |
CN116492333A (zh) | 土木香内酯在制备治疗脂多糖诱导的急性肺损伤药物中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |