摘要
目的:研究黄芪甲苷对小鼠实验性心室重构的保护作用并从基质金属蛋白酶方面探讨其作用机制。方法:采用连续皮下注射异丙肾上腺素14d诱导小鼠心室重构模型,同时以黄芪甲苷(40,80mg/kg)和阳性对照普萘洛尔(40mg/kg)灌胃给药;超声心动图检测左室舒张末期直径(LVIDd)、左室收缩末期直径(LVIDs)、左室射血分数(EF)、左室短轴缩短率(FS);HE染色光镜下观察心肌组织的病理学改变;RT-PCR法检测基质金属蛋白酶MMP2、MMP9及其抑制剂TIMP1、TIMP2的mRNA表达,明胶酶谱法分析MMP2、MMP9的活性。结果:与正常对照组相比,模型组LVIDd、LVIDs均显著升高,EF、FS均明显降低,心肌有纤维化样损伤,表明发生了左室重构;另外,模型组MMP2、MMP9mRNA表达和酶活性均显著增高,而TIMP1、TIMP2mRNA表达在各组均无明显变化。与模型组相比,黄芪甲苷可显著降低LVIDd、LVIDs,增加EF、FS,减轻心肌损伤,下调MMP2、MMP9mRNA表达和酶活性。结论:黄芪甲苷可通过抑制MMP2、MMP9表达及活性,有效逆转心室重构,改善心功能。
Aim：To study the effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect.Method：Ventricular remodeling in mice was induced by consecutively subcutaneous injection of isoproterenol for 14 days.Astragaloside IV（40,80 mg/kg）and propranolol（40 mg/kg,positive control）were administered by gavage to mice.Echocardiography was used to observe the left ventricular end diastolic diameter（LVIDd）,left ventricular end systolic diameter（LVIDs）,fractional shortening（FS）and ejection fraction（EF）.The myocardial pathological pattern was detected by HE staining.Expressions of matrix metalloproteinases（MMP2,MMP9）and tissue inhibitor of metalloproteinases（TIMP1,TIMP2）mRNA in myocardium were detected by RT-PCR.Activities of MMP2 and MMP9 were assayed by zymography.Results：Compared with those of control mice,LVIDd and LVIDs were increased,FS and EF were decreased in the model group.Myocardial injury and fibrosis existed in histop at hological slices of the model group.In addition,the mRNA expressions and activities of MMP2 and MMP9 were increased in the model group.However,there were no markable changes to TIMP1 and TIMP2.Treatment with astragaloside IV reduced LVIDd and LVIDs,increased FS and EF,attenuated myocardial injury,and down-regulated mRNA expressions and activities of MMP2 and MMP9 compared with the model group.Conclusion：Astragaloside IV can greatly improve ventricular remodeling and dysfunction via decreasing MMP2 and MMP9 mRNA expression and activities in cardiac ventricles.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2010年第1期70-75,共6页
Journal of China Pharmaceutical University
关键词
黄芪甲苷
异丙肾上腺素
心室重构
基质金属蛋白酶
astragaloside IV
isoproterenol
ventricular remodeling
matrix metalloproteinase
