目的 观察不同剂量养心氏片对Wistar大鼠急性心肌梗死后梗死区血管新生的影响。方法 将周龄为10周,体重为200~250 g的Wistar雄性大鼠60只,随机分为5组:A组:瑞舒伐他汀组(0.75 mg·kg-1·d-1),B组:高剂量养心氏片组(0.27 g·kg-1·d-1),C组:中剂量养心氏片组(0.18 g·kg-1·d-1),D组:低剂量养心氏片组(0.09 g·kg-1·d-1),E组:生理盐水对照组。各组灌胃4周后,结扎大鼠冠状动脉前降支制作大鼠急性心肌梗死模型,术后继续灌胃,并于4周后采外周血行血脂(总胆固醇、甘油三酯、低密度脂蛋白胆固醇等)、肝肾功等生化化验,处死大鼠,取心肌组织行组织切片HE染色观察心肌梗死区相关的病理学变化,提取梗死区及缺血区心肌组织蛋白,行免疫组化检测血管内皮生长因子(VEGF)的表达。结果 4周后处死的大鼠心肌HE染色切片显示,用药组大鼠心肌组织HE染色切片都可见大量存活岛状心肌细胞及新生的薄壁毛细血管,生理盐水对照组大鼠心肌组织HE染色切片可见较少的正常心肌细胞,毛细血管基本消失。免疫组化检测结果显示,高剂量养心氏片用药组VEGF蛋白表达量较中、低剂量组及对照组均显著增加,差异具有统计学意义(P<0.05);与瑞舒伐他汀相比,中、高剂量养心氏片用药组VEGF蛋白表达量显著增加,差异具有统计学意义(P<0.05)。结论 养心氏片具有明显的促进VEGF蛋白表达及缺血区心肌血管生成的作用,且其作用与剂量呈正相关,中、高剂量养心氏片较瑞舒伐他汀具有更强的促进VEGF蛋白表达及缺血区心肌血管生成的作用。
Abstract
OBJECTIVE To investigate the influence and mechanism of different doses of Yangxinshi on infarction region angiogenesis of Wistar rats after acute myocardial infarction. METHODS Sixty healthy male Wistar rats were randomly divided into five groups, named as follow:group A: rosuvastatin group (0.75 mg·kg-1·d-1), group B: high-dose Yangxinshi(0.27 g·kg-1·d-1),group C:mid-dose Yangxinshi group (0.18 g·kg-1·d-1),group D: Low-dose Yangxinshi group (0.09 g·kg-1·d-1),group E:saline control group. A, B, C, D group was respectively given the drug by gavage, group E received normal saline by gavage. The models of acute myocardial infarction can be established in the forth week . After continued drugs for 4 weeks, rats were killed before detected blood biochemicalindexes such as blood lipids, liver and kidney function. Myocardial tissue was sliced and stained infarcted myocardium by HE to observe the pathological changes, also extract ischemic and infarct myocardium tissue protein and test VEGF protein expression with immunohistochemistry. RESULTS Myocardial tissue HE staining were observed a lot of survival island cardiomyocytes and neonatal thin-walled capillaries in four treatment groups , however,control group exist less normal cardiomyocytes and capillaries mainly disappear. Immunohistochemistry RESULTS showed high-doses of Yangxinshi group express higher VEGF protein compared with mid-dose group, low-dose group and control group, the difference was statistically significant (P<0.05), VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference was statistically significant (P<0.05). CONCLUSION Yangxinshi promote production of VEGF protein and angiogenesis of ischemic myocardium ,in addition its role and its dose is positive correlated. VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference is statistically significant (P<0.05).
关键词
养心氏片 /
急性心肌梗死 /
血管内皮生长因子 /
血管新生
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Key words
Yangxinshi /
acute myocardial infarction /
VEGF /
region angiogenesis
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中图分类号：
R944
R965
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