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2型糖尿病(T2DM)是一种以高血糖为特征的慢性代谢性疾病,主要是由于胰岛素分泌不足而导致的空腹血糖升高[1]。冠状动脉粥样硬化性心脏病(CHD,简称冠心病)是一种常见的心血管疾病,主要是由于冠状动脉的粥样性硬化引起的血管阻塞或管腔狭窄,从而导致心肌缺血或缺氧性坏死,进而影响心脏功能[2]。近年来,T2DM的患病人数不断增加。据相关不完全统计,预计到2045年,全球T2DM患病人数将增加至7.83亿,已成为全球关注的重要人类问题之一[3]。目前,我国60岁以上的老年人中T2DM患病率超过20%,其中心血管疾病是最常见的并发症,而CHD则是T2DM患者最常见的致残或致死原因[4, 5]。有研究表明,T2DM患者发生心血管疾病的概率是非T2DM人群的2~4倍,葡萄糖耐受量受损是影响CHD进展的重要因素[6]。由此可见,T2DM与CHD相互影响,相互促进。
中药复方制剂麝香保心丸源于宋代《太平惠民和剂局方》中治疗“寒闭证”的经典名方苏合香丸,由戴瑞鸿教授在1972年改良而来。麝香保心丸已在临床应用40余年,方中麝香通窍温阳、活血化瘀为君药;苏合香辟秽通窍、人参扶正益气为臣药;牛黄开窍醒神、肉桂助阳通脉、蟾酥开窍止痛为佐药;冰片开窍醒神为使药。全方寒温并用、通补兼施、益气强心,主要用于治疗气滞血瘀所致的胸痹,症见心前区疼痛固定不移,心肌缺血所致的心绞痛、心肌梗死等[7-9]。目前临床上将麝香保心丸与基础西药中的降糖药联合应用,表现出比单用降糖药更好的血糖调节效果[10],还可以降低患者血清胆固醇水平[11],显著降低心血管事件发生率[12]。但目前关于麝香保心丸“异病同治”T2DM和CHD共同作用机制的研究相对不足。本研究旨在通过运用网络药理学方法,探索麝香保心丸“异病同治”T2DM和CHD的共同作用机制,为今后的研究和应用提供理论依据。
Mechanisms of Shexiang Baoxin Pill in homo-therapy for heteropathy in type 2 diabetes mellitus and coronary heart disease based on network pharmacology
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摘要:
目的 基于网络药理学方法研究麝香保心丸“异病同治”2型糖尿病(T2DM)和冠心病(CHD)的作用机制。 方法 运用中药系统药理学数据库与分析平台(TCMSP)、中药成分数据库(TCMID)、中医药百科全书数据库(ETCM)和BATMAN-TCM数据库筛选麝香保心丸中七味中药的化学成分和作用靶点,利用DisGeNET和GeneCards数据库获取与CHD和T2DM相关的疾病靶点。运用Cytoscape3.8.2软件构建“药物-成分-靶点”网络图,利用STRING数据库构建蛋白互作(PPI)网络图,利用DAVID在线数据库对麝香保心丸治疗T2DM和CHD的共同作用靶点进行GO生物过程分析和KEGG通路富集分析。 结果 共筛选出麝香保心丸治疗T2DM和CHD的潜在活性成分101个,对应229个靶点。网络分析结果表明,麝香保心丸治疗T2DM和CHD的共同主要成分可能是鹅去氧胆酸、熊去氧胆酸、肉桂醛、胆汁酸、肉桂酸及人参皂苷类成分。通路富集分析结果显示,麝香保心丸“异病同治”T2DM和CHD的作用机制可能与抑制炎症反应和氧化应激有关。 结论 麝香保心丸可通过多成分、多靶点、多途径发挥“异病同治”T2DM和CHD的作用,为麝香保心丸的临床应用及进一步研究提供理论基础。 Abstract:Objective To probe into the mechanism of Shexiang Baoxin Pill in homo-therapy for heteropathy for type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) based on network pharmacology. Methods All chemical components and action targets of these seven traditional Chinese medical in Shexiang Baoxin Pill were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM platform, and the DisGeNET and GeneCards databases were used to obtain CHD and T2DM-related Disease targets. The “drug-component-target” network map was constructed by Cytoscape 3.8.2 software, the protein-protein interaction (PPI) network map was constructed by STRING database, and the GO biological process analysis and KEGG pathway enrichment analysis were performed on the common targets of Shexiang Baoxin Pill for T2DM and CHD using DAVID online database. Results A total of 101 potential active ingredients for the treatment of T2DM and CHD in Shexiang Baoxin Pill were screened out, corresponding to 229 targets. Network analysis results showed that the common main active ingredients in Shexiang Baoxin Pill for treating T2DM and CHD might be chenodeoxycholic acid, ursodeoxycholic acid, cinnamic aldehyde, bile acids, cinnamic acid, and ginsenosides. The results of pathway enrichment analysis showed that the mechanism of action of Shexiang Baoxin Pill in the treatment of type 2 diabetes and coronary heart disease in treating T2DM and CHD might be related to the inhibition of inflammatory response and oxidative stress. Conclusion Shexiang Baoxin Pill could play a role in treating CHD and T2DM through multiple components, multiple targets and multiple pathways, which provided a certain theoretical basis for the clinical application and further research of Shexiang Baoxin Pill. -
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