血府逐瘀胶囊对急性心肌梗死再灌注后心肌及内皮素-1、一氧化氮／一氧化氮合酶体系影响的实验研究

目的：观察血府逐瘀胶囊对急性心肌梗死（acute myocardial infarction．AMI）再灌注后心肌组织及一氧化氮（nitric oxide,NO）／一氧化氮合酶（nitric oxide synthase．NOS）体系和内皮素-1（endothelin-1，ET-1）的影响，探讨其改善血管内皮功能的机制。方法：Yorkshire猪45只，随机分成假手术组、模型对照组和血府逐瘀胶囊治疗组。开胸结扎左冠状动脉前降支90min后，松解2h制备AMI再灌注模型。测定造模前后和再灌注后血清ET-1和NO的含量；冠状动脉造影观察心肌血流恢复情况；Western blot分析心肌组织内皮型一氧化氮合酶（endothelial nitric oxide synthase，eNOS）和ET—1蛋白表达；病理学分析心肌组织形态变化。结果：血府逐瘀胶囊组造模后和再灌注后血ET-1水平低于模型组（P〈0．01），而NO表达水平明显高于模型组（P〈0．01）。冠状动脉造影提示治疗组冠状动脉血流通畅情况优于对照组，但结果没有统计学意义（P=0．253）。Western blot显示血府逐瘀胶囊组eNOS蛋白表达较模型组有所提高。ET-1蛋白表达则有所下降（P〈0．01）。HE染色及微血管密度分析显示与模型对照组相比，血府逐瘀胶囊组毛细血管扩张程度明显减轻。心肌组织损伤明显改善，微血管密度明显增加。结论：内皮细胞受损可能是无再流现象发生的重要机制之一．血府逐瘀胶囊可能通过调控NO和ET-1基因表达来达到对AMI的治疗作用。

Effects of Xuefu Zhuyu Capsule on endothelin-1 release in myocardium and vascular endothelium and nitric oxide/nitric oxide synthase system of swines after acute myocardial infarction and reperfusion

OBJECTIVE: To observe the effects of Xuefu Zhuyu Capsule (XFZYC), a compound traditional Chinese herbal medicine, on endothelin-1 (ET-1) release in myocardium and vascular endothelium and nitric oxide (NO)/nitric oxide synthase (NOS) system of swines after acute myocardial infarction (AMI) and reperfusion, and to explore the action mechanisms of XFZYC in improving the endothelium function. METHODS: Forty-five Yorkshire swines were randomized into 3 groups: sham-operated group, untreated group and XFZYC-treated group. A Yorkshire swine model of reperfusion in AMI was established by ligation of left anterior descending coronary artery for 90 min followed by 2 h relaxation. The content of serum ET-1 and NO was measured by radioimmunoassay before and after AMI and after reperfusion, respectively. Twenty-four hours after operation, all Yorkshire swines underwent diagnostic coronary angiography to delineate coronary arteries. The expressions of ET-1 and endothelial nitric oxide synthase (eNOS) in myocardial tissue of ischemic area were quantified with Western blotting. Microvessel density of the implanting sites was assessed by using HE staining. RESULTS: Compared with the untreated group, the levels of serum ET-1 after AMI and reperfusion were significantly decreased in XFZYC-treated group (P<0.01), while the NO levels after AMI and reperfusion in XFZYC-treated group were significantly increased (P<0.01). There was no significant difference in diagnostic coronary angiography between XFZYC-treated group and untreated group (P=0.253). Western blotting showed that the level of ET-1 in ischemic area in XFZYC-treated group was lower than that in the untreated group (P<0.01), while the eNOS protein expression in XFZYC-treated group was higher than that in the untreated group (P<0.01). The results of HE staining and microvessel density analysis of the implanting sites all showed that the degree of telangiectasis was reduced, the cardiac muscle damage was improved, and the density of capillaries was increased obviously in XFZYC-treated group as compared with the untreated group. CONCLUSION: The endothelium injury may be one of the important mechanisms for no-reflow phenomenon. XFZYC may reduce the no-reflow by protecting endothelium cells.