麝香通心滴丸通过p-Akt/p-GSK3β/GSK3β通路对心肌梗死小鼠的心肌保护作用研究

Protective Effect of Shexiang Tongxin Dropping Pills(麝香通心滴丸)on Myocardium of Myocardial Infarction Mice through p-Akt/p-GSK3β/GSK3β Pathway

目的:研究麝香通心滴丸对于心肌梗死小鼠的心肌保护作用及其与p-Akt/p-GSK3β/GSK3β(磷酸化蛋白激酶B/磷酸化糖原合酶激酶3/糖原合酶激酶)通路的相关性。方法:将70只C57小鼠随机分为5组,分别为正常组(Control),心肌梗死组(Myocardial,MI),麝香通心滴丸小剂量组(MSM1),麝香通心滴丸中剂量组(MSM2),麝香通心滴丸高剂量组(MSM3),MI组与MSM各组制备心肌梗死模型,MSM各组在复制心梗模型前4周每日灌胃不同剂量的麝香通心滴丸,心脏彩超测定比较各组小鼠心功能,HE染色观察各组小鼠心肌组织病理变化,蛋白免疫印迹法测定各组小鼠心梗区心肌组织p-Akt,p-GSK3β蛋白的表达。结果:心脏彩超结果显示,MSM各组相较于MI组,LVEDd、LVESd、ExLVDd、FS 4项心功能指标均出现提升(均P<0.05),此外,MSM2组相较于MSM1组及MSM3组相较于MSM2组,心功能指标LVEDd、LVESd、ExLVDd、PWs、FS出现渐进性改善(均P<0.05);HE染色显示,相较于MI组,MSM各组随着麝香通心滴丸剂量增高,镜下可见的坏死损害心肌细胞逐渐减少;Western blot分析显示,MSM各组相较于MI组,p-Akt、p-GSK3β的表达量明显增加(均P<0.05),随着麝香通心滴丸剂量增加,p-Akt、p-GSK3β的表达量均出现渐进性增加(均P<0.05)。结论:麝香通心滴丸可有效发挥小鼠心梗后的心肌保护作用,其机制可能与激活p-Akt/p-GSK3β/GSK3β通路表达相关。

Objective:To research the protective effect of Shexiang Tongxin Dropping Pills on myocardium of myocardial infarction mice and its correlation with p-Akt/p-GSK3β/GSK3βpathway.Methods:Seventy C57 mice were randomly divided into five groups:control group,myocardial infarction group(MI),low-dose Shexiang Tongxin Dropping Pill group(MSM1),medium-dose Shexiang Tongxin Dropping Pill group(MSM2),high-dose Shexiang Tongxin Dropping Pill group(MSM3).Myocardial ischemia model was established in MI group and MSM group.Shexiang Tongxin Dropping Pills of different doses were given daily to MSM group four weeks before the establishment of myocardial infarction model.Cardiac function was measured by color Doppler echocardiography,myocardial tissue changes were observed by HE staining,and the expression of p-Akt and p-GSK3βprotein in myocardial tissue of myocardial infarction was determined by Western blotting.Results:Compared with MI group,the four cardiac function indexes of MSM group were increased(all P<0.05),including LVEDd,LVESd,ExLVDd and FS.In addition,with the increase of the concentration of Shexiang Tongxin Dropping Pill,the cardiac function indexes such as LVEDd,LVESd,ExLVDd,PWs and FS improved gradually(all P<0.05).By HE staining,compared with MI group,with the dose of Shexiang Tongxin Dropping Pills increasing,myocardial necrosis and damage gradually decreased in MSM group.Western blot analysis showed that the expression of p-Akt and p-GSK3βin MSM groups increased significantly compared with MI group(all P<0.05).The expression of p-Akt and p-GSK3βincreased progressively with the increase of dose of Shexiang Tongxin Dropping Pills(all P<0.05).Conclusion:Shexiang Tongxin Dropping Pills effectively protected the myocardium of mice after myocardial infarction,and its mechanism may be related to activating the expression of p-Akt/p-GSK3β/GSK3βpathway.