王琛 王亚红

摘要 目的：探讨四妙勇安汤对冠心病痰瘀互结证大鼠的心肌保护作用及机制。方法：建立冠心病痰瘀互结证大鼠模型，随机分为正常对照组、模型组、四妙勇安汤大剂量组、四妙勇安汤中剂量组、四妙勇安汤小剂量组，相应干预后，处理动物。检测血脂三项、凝血三项、肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、内皮素-1（ET-1）及可溶性血管细胞黏附分子-1（sICAM-1）;采用TUNEL法检测心肌细胞凋亡率;Western blotting法检测心肌组织凋亡及自噬相关蛋白的表达。结果：与模型组比较，四妙勇安汤可降低血清总胆固醇（TC）、三酰甘油（TG）及低密度脂蛋白（LDL）含量（P<0.05），同时可增加血浆活化部分凝血活酶时间（APTT）（P<0.05）;降低血清炎症介质TNF-α、IL-8及ET-1、sICAM-1含量（P<0.05）;四妙勇安汤干预组可有效降低心肌细胞凋亡率、促进抗凋亡蛋白BCL-2及抑制促凋亡蛋白BAX的表達;并且抑制自噬相关蛋白LC3、Beclin-1表达，与模型组比较，差异均有统计学意义（P<0.05）。结论：四妙勇安汤具有改善冠心病痰瘀互结证大鼠血脂、血凝及内皮功能等作用，具有保护受损心肌的作用，其机制可能与抑制自噬引起的心肌细胞凋亡有关。

关键词 四妙勇安汤;冠心病;痰瘀互结证;大鼠模型;心肌损伤;保护作用;自噬;细胞凋亡

Abstract Objective：To explore the myocardial protective effects and mechanism of Simiao Yongan Decoction on rats with coronary heart disease with mutual syndrome of phlegm and blood stasis.Methods：The rat model of coronary heart disease of phlegm and blood stasis syndrome was established and were randomly divided into a normal control group，a model group，Simiao Yongan Decoction of high，middle and small dose group.After the corresponding intervention，we handled the animals，detected 3 blood lipids，3 blood coagulation，tumor necrosis factor-α（TNF-α），interleukin-8（IL-8），endothelin-1（ET-1） and soluble vascular cell adhesion molecule-1（sICAM-1）; TUNEL method was used to detect myocardial cell apoptosis rate; Western blotting method was used to detect myocardial tissue apoptosis and the expression of autophagy-related proteins.Results：Compared with the model group，Simiao Yongan Decoction groups can reduce serum total cholesterol，triglycerides and low-density lipoprotein content（P<0.05），and increase plasma activated partial thromboplastin time（APTT）（P<0.05）; reduce serum inflammatory factors TNF-α，IL-8 and ET-1，sICAM-1 content（P<0.05）; Simiao Yongan Decoction intervention group can effectively reduce the rate of cardiomyocyte apoptosis，promote anti-apoptotic protein BCL-2 and inhibit the expression of pro-apoptotic protein BAX; inhibit the expression of autophagy-related proteins LC3 and Beclin-1，which were significantly different compared with the model group（P<0.05）.Conclusion：Simiao Yongan Decoction can improve coronary heart disease with phlegm and blood stasis syndrome rats′ blood lipids and coagulation，as well as endothelial dysfunction.Moreover the mechanism may probably be related with suppression autophagy-related apoptosis.

Keywords Simiao Yongan Decoction; Coronary heart disease; Phlegm and blood stasis syndrome; Rat model; Myocardial injury; Protective effects; Autophagy; Apoptosis

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.07.011

冠心病仍是全球范围内第一位致死、致残原因，占全球总死亡人数的30%。本病相当于中医的“胸痹”“心痛”，为本虚标实之证。气血阴阳亏虚为本，痰浊、瘀血、气滞、寒凝为标。西医学认为动脉粥样硬化及心肌缺血是冠心病主要的病理特征，动脉粥样硬化主要由脂代谢紊乱引起，为中医学“痰”的表现，心肌缺血导致血流运行缓慢，为中医学“瘀”的表现，越来越多的研究表明冠心病痰瘀互结证是目前冠心病较常见且病变程度较严重的证型[1-5]。

痰瘀同治法是目前治疗冠心病痰瘀互结证的常用方法，但其临床疗效评价尚待进一步明确[6]。陈可冀院士等认为痰瘀日久，因瘀致毒，痰、瘀、毒互结为冠心病病情发展与恶化的关键所在[7]，在治疗中注重“化毒”。……