补肾活血复方调控Wnt通路抑制心力衰竭心肌损伤及细胞凋亡的机制研究  

Mechanism of Bushen Huoxue Recipe(补肾活血复方)Regulating Wnt Signal Pathway to Inhibit Myocardial Injury and Apoptosis in Heart Failure

作　　者：何佳[1] 付博[2] 张艳[2] 卢秉久[2] HE Jia;FU Bo;ZHANG Yan;LU Bingjiu(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中华中医药学刊》2023年第7期65-69,I0013,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81774157)。

摘　　要：目的 研究补肾活血复方通过抑制Wnt信号通路(Wingless)抑制心力衰竭大鼠心肌损伤及细胞凋亡的分子机制。方法 将45只斯泼累格·多雷(Sprague-Dawley, SD)大鼠随机分为假手术组、模型组、补肾活血复方组及赖诺普利组。采用结扎冠状动脉配合力竭式游泳构建心力衰竭模型。造模成功后按照实验分组利用补肾活血复方或赖诺普利给予大鼠持续灌胃4周。治疗结束后,采用彩色超声多普勒心动图评价大鼠心功能,称取体质量(body weight, BM)及左心室湿质量(left ventricular wet mass, LVM),计算左心室质量指数(left ventricular mass index, LVMI),苏木精-伊红(hematoxylin-eosin, HE)染色检测心肌病理组织学损伤,蛋白质印迹(Western blot)检测BCL2凋亡调节器(BCL2 apoptosis regulator, Bcl-2)、BCL2相关X,凋亡调节器(BCL2 associated X,apoptosis regulator, Bax)、活化半胱天冬酶3(cleaved-caspase-3)、Wnt家族成员3A(wnt family member 3A,Wnt3a)、β-连环蛋白(β-catenin)蛋白表达,实时荧光定量聚合酶链式反应(real-time PCR)检测Bcl-2、Bax、半胱天冬酶3(Caspase-3)、Wnt3a、β-catenin mRNA表达。结果 与假手术组比,模型组的左心室舒张末内径(left ventricular end diastolic diameter, LVEDD)及左心室收缩末内径(left ventricular end systolic diameter, LVESD)、LVMI、Bax、Wnt3a、β-catenin蛋白及mRNA,cleaved-caspase-3蛋白,Caspase-3 mRNA表达均显著上调,左室短轴缩短率(left ventricular short axis shortening rate, LVFS)、左心室射血分数(left ventricular ejection fraction, LVEF)、Bcl-2蛋白及mRNA,cleaved-caspase-3蛋白,Caspase-3 mRNA表达均显著下调,差异均有统计学意义(P<0.05);与模型组比,补肾活血复方组及赖诺普利组LVEDD、LVESD、LVMI、Bax、cleaved-caspase-3、Wnt3a、β-catenin蛋白及mRNA表达显著下调,LVFS、LVEF、Bcl-2蛋白及mRNA表达显著上调,差异均有统计学意义(P<0.05)。假手术组心肌细胞形态正常,肌纤维排列整齐,结构清�Objective To study the molecular mechanism of Bushen Huoxue Recipe(补肾活血复方)inhibiting cardiomyocyte apoptosis in rats with heart failure by inhibiting Wnt signal pathway.Methods Forty-five Sprague-Dawley(SD)rats were randomly divided into sham-operation group,model group,Bushen Huoxue Recipe group and lisinopril group,with 10 rats in each group.The model of heart failure was established by ligating coronary artery and exhaustive swimming.After the model was successfully established,the rats were given Bushen Huoxue Recipe or lisinopril for 4 weeks according to the experimental grouping.After the treatment,the cardiac function of rats was evaluated by color Doppler echocardiography.The body weight(BM)and left ventricular wet mass(LVM)were weighed,and the left ventricular index(LVMI)was calculated.Histopathological damage of myocardium was detected by hematoxylin-eosin(HE)staining,and Bcl-2,Bax,cleaved-caspase-3,Wnt3a and β-catenin proteins were detected by Western blot.The mRNA expressions of Bcl-2,Bax,caspase-3,Wnt3a and β-catenin were detected by Real-time PCR.Results Compared with those of the sham-operated group,the expressions of left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),LVMI,Bax,Wnt3a,β-catenin protein and mRNA cleaved-caspase-3 protein,Caspase-3 mRNA in the model group were significantly increased,while the left ventricular short axis shortening rate(LVFS),left ventricular ejection fraction(LVEF),Bcl-2 protein and mRNA cleaved-caspase-3 protein,Caspase-3 mRNA were significantly decreased.Compared with those of the model group,the expressions of LVEDD,LVESD,LVMI,Bax,Wnt3a,β-catenin protein and mRNA in the Bushen Huoxue Recipe group and the lisinopril group were significantly down-regulated,while the expressions of LVFS,LVEF,Bcl-2 protein and mRNA were significantly up-regulated with statistical significance(P<0.05).In the sham-operation group,the morphology of myocardial cells was normal,the muscle fibers were arranged neatly and the structure

关 键 词：补肾活血复方 WNT通路 心力衰竭 心肌损伤 心肌细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]