补肾活血方对心肌梗死大鼠心肌修复作用及机制探讨

Mechanism on Repairing Effect with Bushen Huoxue Formula in Myocardial Infarction Rats

目的:观察不同剂量补肾活血方对异丙肾上腺素所致心肌梗死大鼠内皮祖细胞(EPCs)的动员作用及其对缺血心肌组织的损伤修复作用,并探讨可能的作用机制。方法:雄性SD大鼠48只随机分为对照组、模型组、辛伐他汀组、补肾活血方低、中、高剂量组,皮下注射异丙肾上腺素造模后检测各组外周血EPCs数量、HE染色及TTC染色观察病理改变、心肌组织中Notch1蛋白表达及心肌组织中CD+34蛋白表达。结果:补肾活血方各剂量组及辛伐他汀组均可见外周血EPCs数量增多(P<0.01),心肌缺血损伤程度减轻,心肌组织中CD+34含量增多,且Notch1蛋白表达量较模型组明显增多,补肾活血方中高剂量组作用明显。结论:补肾活血方有可能通过激活Notch信号通路,动员心肌梗死大鼠EPCs,促进血管新生,从而达到修复受损心肌的作用。

Objective：To observe the effects of different doses of Bushen Huoxue Formula （BSHXF） and simvastatin （15 rag/ kg） on the mobilization of endothelial progenitor cells （EPCs） in rats with myocardial infarction induced by isoproterenol, and al so how to repair the injured myocardial tissues, and to explore the possible mechanism. Methods：42 Sprague Dawley male rats were randomly divided into six groups;normal group, model group, simvastatin group, BSHXF low dose group, BSHXF middle dose group,BSHXF high dose group. All rats were injected with isoproterenol （10 mg/kg） on t9th,20th,21st day,except for the normal group. Electrocardiograph was monitored to confirm the diagnosis of acute myocardia infarction model rats. EPCs＇ num ber in peripheral blood was measured with flow cytometer on 22nd days. Histopathological examination and TFC assay of heart tis sues were performed. The expressions of Notchl and Jaggedl in the heart tissues were detected by Western blotting. The changes of the CD34 and RBPJ in tissues were tested by immunohistochemical method. Results ： The numbers of EPCs in simvastatin group and BSHXF each dose groups increased（P 〈 0. 01 ）. The degree of myocardial ischemia injury alleviated and CD34 positive cells increased in simvastatin group and BSHXF each dose groups in histological observation. The Notchl and Jaggedl protein ex pression increased significantly in simvastatin group and BSHXF middle dose group and BSHXF high dose group. Conclusion ： The repair effect of BSHXF in myocardial infarction may be related to the promotion the mobilization of EPCs ,which may lead to neovascularisation and result in the reduced myocardial injury. The angiogenesis effects may through the activation of Notch signa ling pathway.