冠心丹参滴丸对缺血心肌AMPK-解偶联蛋白2的调控作用

The Modulation of AMPK-uncoupling Protein 2 in Ischemia Myocardium by Guanxindanshen Dropping Pills

目的探讨冠心丹参滴丸对缺血心肌收缩功能的影响及其作用机制。方法通过开胸置入Ameroid缩窄环的方法建立猪缺血心肌模型,设假手术组、模型组、冠心丹参滴丸(GXDS)组、盐酸曲美他嗪(TMZ)组,观察4组心肌结构改变和心脏功能改变,检测心肌中能量参数水平和线粒体内膜解偶联蛋白2(uncoupling protein 2,UCP2)及其上游腺苷一磷酸活化蛋白激酶(AMPK)的基因和蛋白水平。结果心肌缺血会导致心肌收缩功能障碍,模型组射血分数、短轴缩短率和室壁增厚率均较假手术组降低,GXDS组和TMZ组射血分数、室壁增厚率较模型组增高,差异有统计学意义(P<0.05)。与假手术组比较,模型组心肌的三磷酸腺苷(ATP)降低,二磷酸腺苷(ADP)水平升高,差异均有统计学意义(P<0.05),而AMP未见明显降低,总腺苷酸含量和能荷较假手术组降低,GXDS组和TMZ组ATP、能荷较模型组增高,差异有统计学意义(P<0.05)。模型组AMPK和UCP2的蛋白表达水平和mRNA水平均升高,AMPK的磷酸化比例增高,GXDS和TMZ可以改善缺血引起的UCP2和AMPK的增高,减少AMPK磷酸化。结论冠心丹参滴丸可以改善缺血心肌的收缩功能,减少AMPK的激活和UCP2的水平。

Objective To observe the effects of Guanxindanshen drop pills on AMPK-uncoupling protein 2 of ischemic myocardium.Methods The pig ischemic myocardium models by placing ameroid constrictors were divided into sham group,model group,Guanxindanshen drop pills(GXDS)group and Trimetazidine(TMZ)group.The myocardial structure,cardiac function,levels of energy parameters,genes and proteins of uncoupling protein 2(UCP2)and its upstream AMPK were detected.Results Ejection fraction,fractional shortening and ventricular wall thickening in the model group were significantly decreased than those in the sham group.Ejection fraction,and ventricular wall thickening were increased in the GXDS group and TMZ group compared with those in the model group.The levels of adenosine triphosphate(ATP),the total adenosine acid content and energy charge in the myocardium of the model group were decreased than those in the sham group.The levels of ATP,and energy charge were increased in the GXDS group and TMZ group compared with those in the sham group.In the model group,protein expression and mRNA levels of adenosine monophosphate activated protein kinase(AMPK)and UCP2 were increased,and AMPK phosphorylation rate was increased.The ischemia-induced increase of UCP2 and AMPK,and reduce AMPK phosphorylation,were improved by GSDS and TMZ.Conclusion Guanxindanshen drop pills could improve the systolic function of ischemic myocardium,reduce AMPK activation and UCP2 levels.