芪苈强心胶囊通过抑制血管紧张素Ⅱ改善压力超负荷致小鼠心肌肥厚  

Qiliqiangxin Capsules ameliorate Pressure Overload-Induced Cardiac Hypertrophy in mice via reducing the expression of AngiotensinⅡ

作　　者：叶勇 李磊[2] 蒋国良 吴剑[2] 周宁[3] 马宏[4] 关爱丽[2] 龚惠 葛均波 邹云增[1,2] 

机构地区：[1]复旦大学生物医学研究院,上海200032 [2]复旦大学附属中山医院上海市心血管病研究所,上海200032 [3]华中科技大学同济医学院附属同济医院心内科,武汉430030 [4]浙江大学医学院附属第二医院心内科,杭州310009

出　　处：《中国分子心脏病学杂志》2011年第6期355-361,共7页Molecular Cardiology of China

基　　金：国家自然基金重点项目(30930043);国家自然基金青年基金项目(81000041);上海市重点专项课题(08dj1400504)

摘　　要：目的探讨探讨芪苈强心胶囊是否通过抑制血管紧张素Ⅱ(AngⅡ)表达改善压力超负荷下小鼠心肌肥厚。方法小鼠行升主动脉缩窄手术(TAC)建立心肌肥厚模型,8-10周龄野生型雄性小鼠(WT)和雄性血管紧张素原基因敲除小鼠(ATG-/-)随机分为假手术组、生理盐水组、芪苈强心胶囊三组,TAC组小鼠给予生理盐水或1.0mg/(kg.d)药物灌胃处理。术后2周行心超及血流动力学检查,同时分析心肌组织学指标以及肥厚相关基因表达,酶联免疫吸附法(ELISA)检测血浆和心肌组织AngⅡ浓度,,蛋白印迹法检测磷酸化细胞外信号调节激酶(p-ERK)及血管紧张素Ⅱ-1型(AT1)受体表达。结果 WT和ATG-/-小鼠TAC后2周,主动脉血压及左室收缩末期压显著升高,芪苈强心胶囊对其均无影响。WT小鼠中,此药显著抑制TAC介导AngⅡ的升高(P<0.05),抑制TAC介导的左室前壁,左室后壁增厚以及心肌细胞横截面积(CSA)和纤维化面积增大,同时抑制肥厚相关基因、AT1受体和p-ERK表达上调(P<0.05),;ATG-/-小鼠中,在AngⅡ缺失的情况下,TAC两组间左室前后壁、CSA、纤维化面积以及肥厚相关基因、AT1受体和p-ERK表达无明显差异(P>0.05)。结论芪苈强心胶囊改善压力超负荷致小鼠心肌肥厚是通过抑制AngⅡ表达来减弱AT1受体激活,非直接抑制压力超负荷机械刺激引起AT1受体的激活。Objective To investigate whether downregulation of AngiotensinⅡwas involved in the mechanism by which Qiliqiangxin Capsules inhibits the pressure overload-induced cardiac hypertrophy in mice. Methods Pressure-overload model was established in 8-10 weeks old wild type (WT) and angiotensinogen-deficient (ATG-/-) (lacking endogenous Ang II) male mice performed with Transverse Aorta Constricting (TAC) surgery for 2 weeks. All the mice were treated with Sham or TAC operation, and all TAC mice was administered with saline or Qiliqiangxin Capsules (1.0mg/kg.d) through gastric tube. Echocardiography and hemodynamic measurement were performed at 2 weeks after TAC. And cardiac histology and hypertrophic gene expression was analyzed. AngⅡlevels in serum and myocardium were measured by ELISA. The expression of AT1 receptor and phosphorylation of ERK were detected by western blot method. Results TAC for 2 week induced apparently cardiac hypertrophy marked by distinguished elevated aorta blood pressure(ABP) and left ventricle end-systolic pressure(LVESP) , Qiliqiangxin Capsules had no significant effect on them both in WT and ATG-/- mice. In WT mice, Qiliqiangxin Capsules greatly suppressed the increase of AngII level in serum and myocardium,and it also abolished the upregulation of hypertrophic gene,AT1 receptor and p-ERK expression. Besides,it significantly supressed cardiac hypertrophy characterized by enhanced left ventricular anterior wall at end-diastolic( LVAWd), left ventricular posterior wall at end-diastolic(LVPWd), cross-sectional area(CSA) and fibrotic area in WT mice(P<0.05). In ATG-/- mice,however,with the absence of AngII, The two TAC group mice showed no striking diffrence in LVAWd, LVPWd ,CSA, fibrotic area and hypertrophic gene,AT1 receptor ,p-ERK expression(P>0.05). Conclusions Qiliqiangxin Capsules ameliorate pressure overload-induced cardiac hypertrophy through the inhibiting the secretion of AngⅡ, which in turn, attenuated the expression of AT1 receptor. It could not directly affect the expression o

关 键 词：芪苈强心胶囊 血管紧张素Ⅱ 压力超负荷 心肌肥厚 升主动脉缩窄 

分 类 号：R285.5[医药卫生—中药学]