心肌尔康对异丙肾上腺素致小鼠心室重构的保护作用及其机制

目的：研究心肌尔康对异丙肾上腺素致小鼠心室重构的保护作用并探讨其机制。方法：采用连续7d皮下注射小剂量异丙肾上腺素的方法诱导小鼠心室重构模型。小鼠随机分为空白对照组,模型组,心肌尔康低、中、高剂量组,心肌尔康萃取水层组,心肌尔康萃取正丁醇组和美托洛尔组,灌胃给药。实验结束时计算小鼠心脏质量指数,观察心肌病理形态学改变,比色法测定心肌组织中羟脯氨酸含量及血清中超氧化物歧化酶活性和丙二醛含量。结果：与空白对照组相比,模型组小鼠心脏质量指数明显升高（P〈0．01）,血清超氧化物歧化酶活性下降,血清丙二醛含量升高（P〈0．01）。与异丙肾上腺素组相比,心肌尔康能明显降低心脏质量指数（P〈0．01）,改善心肌病理学改变,抑制心肌组织中羟脯氨酸含量的增加（P〈0．05）,提高血清超氧化物歧化酶活性,降低血清丙二醛含量（P〈0．01）。水层成分能明显抑制心肌细胞肥大（P〈0．01）,而正丁醇成分对心肌细胞肥大和心肌纤维化均有明显的抑制作用（P〈0．01）。结论：心肌尔康对异丙肾上腺素诱导的小鼠心室重构具有保护作用,其机制可能与清除氧自由基,提高机体的抗氧化能力有关,而水层组和正丁醇组的药理学效应可能是通过非抗氧化应激途径产生。

Effects of a compound Chinese medicine Xinji' erkang on isoproterenol-induced ventricular remodeling in mice

OBJECTIVE： To investigate the effects of Xinji＇erkang （XJEK）, a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice. METHODS. Isoproterenol was given subcutaneously （1 mg/kg, twice per day for 7 d） to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, XJEK low-, medium- and high-dose groups, XJEK water layer group, XJEK n-butanol layer group and metoprolol group. All drugs were given by intragastric administration. At the end of the 7th day, the hearts of the rats were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight （HW/BW）. The histological changes were observed by hemotoxylin-eosin and Van Gieson staining. Colorimetric method was used to determine the content of hydroxyproline in heart, and the activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in serum. RESULTS. Compared with the isoproterenol injection only, XJEK potently inhibited cardiomyocyte hypertrophy and the increase of hydroxyproline content in heart （P〈0.01）, improved cardiac pathology change, inhibited the decrease of SOD activity and the increase of MDA content in serum （P〈0.01）. XJEK water layer also inhibited the increase of cardiomyocyte hypertrophy （P〈0.01） while XJEK n-butanol layer inhibited cardiomyocyte hypertrophy and fibrosis （P〈0.01）. CONCLUSION： XJEK possesses protective effects against isoproterenol-induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body. XJEK water layer and XJEK n-butanol layer attenuated ventricular remodeling without significant oxidative stress state changing, which indicates that a non-antioxidative stress mechanism may exist.