益气活血方对心肌缺血大鼠Akt/mTOR信号通路的影响  

Influence of Yiqi Huoxue Fang on Akt/mTOR signaling pathway in rats with myocardial ischemia of myocardial infarction

作　　者：刘文臣[1] 郭书文[1] 郑乘龙[1] 王惠[1] 张璐[1] 吴佳妮[1] 刘俊丽[2] 黄小楼[1] 李芳赫 谭晓波[1] 蔡倩[1] 

机构地区：[1]北京中医药大学中医学院,北京100029 [2]北京中医药大学东直门医院脑病3科

出　　处：《北京中医药大学学报》2017年第5期376-384,共9页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81473552;No.81173142)~~

摘　　要：目的依托大鼠心肌缺血模型,探讨蛋白激酶B/雷帕霉素靶蛋白(Akt/m TOR)信号通路在心肌中的表达及益气活血方对其的作用机制。方法 SPF级雄性SD大鼠随机分为模型组、培哚普利组、芪参益气滴丸组、益气活血方组和假手术组,结扎左冠状动脉前降支构建心肌梗死模型,术后第2天灌胃给药。以第7、28天为观测时间点。超声检测各组大鼠心脏功能和结构的变化,HE染色观察心肌病理形态改变,Western blot、RT-PCR法和免疫组化法检测大鼠心肌梗死区边缘Akt、m TOR及磷酸化表达水平。结果第7、28天,与假手术组相比,模型组大鼠心脏左室射血分数(LVEF)、左室短轴率(LVFS)显著降低(P<0.01),第7天模型组大鼠左室收缩末期容积(LVESV)显著升高(P<0.01),第28天模型组大鼠LVESV和左室舒张末期容积(LVEDV)显著增大(P<0.01);与模型组相比,各给药组第28天LVEF、LVFS升高,LVEDV和LVESV显著降低(P<0.01)。模型组梗死区边缘室壁变薄,心肌细胞数量减少,心肌细胞排列紊乱,炎性细胞浸润;各给药组梗死区边缘心肌细胞排列紊乱,心肌细胞数量减少。模型组磷酸化Akt(p-Akt)/Akt、磷酸化雷帕霉素靶蛋白(p-m TOR)/m TOR值增高(P<0.05),Akt、m TOR mRNA表达显著增高(P<0.01),p-Akt、p-m TOR阳性细胞率明显增高(P<0.01);各给药组p-Akt/Akt、p-m TOR/m TOR比值增高(P<0.05),Akt、m TOR m-RNA表达增强(P<0.05或P<0.01),各给药组均可明显提高pAkt、p-m TOR阳性细胞率水平(P<0.05)。结论益气活血方能够改善心肌缺血大鼠心脏功能,可能通过激活心脏自我保护机制Akt/m TOR信号通路产生保护心肌细胞的作用。Objective To investigate the myocardial expressions of protein kinase B（ Akt）/mammalian target of rapamycin（ m TOR） signaling pathway and effective mechanism of Yiqi Huoxue Fang depending on model of myocardial ischemia. Methods The model of acute myocardial infarction（ AMI） was established through ligation of left coronary anterior descending branch in SD rats,and randomly divided into model group,perindopril group,Qishen Yiqi Gutta Pills group,Yiqi Huoxue Fang group and shamoperation group,and all groups were given orally corresponding medications respectively 2 d afteroperation. The observation time points were set on the 7th d and 28 th d. The changes of heart function and structure were detected by using ultrasonic testing,changes of myocardial pathomorphology were observed after HE staining,and expressions of Akt,m TOR,p-Akt and p-m TOR in infarction marginal zone were detected by using Western blot test,real-time fluorescence quantitative polymerase chain reaction（ RTPCR） and immunohistochemistry technique in all groups. Results The level of left ventricular ejection fraction（ LVEF） and left ventricular fraction shortening（ LVFS） decreased significantly in model group compared with sham-operation group on the 7th d and 28 th d（ P〈 0. 01）. The level of left ventricular end-systolic volume（ LVESV） increased significantly on the 7th d（ P〈 0. 01）,and levels of LVESV and left ventricular end-diastolic volume（ LVEDV） increased significantly（ P〈 0. 01） on the 28 th d in model group. The levels of LVEF and LVFS increased and levels of LVEDV and LVESV decreased significantly in all medicated groups compared with model group（ P〈 0. 01）. The thinner ventricular wall,less cardiomyocytes,disorder myocardial cells arrangement and inflammatory cell infiltration were observed in infarction marginal zone in model group, and disorder myocardial cells arrangement and less cardiomyocytes were observed in all medicated groups. The ratio of p-Akt/Akt and p-m TOR/m TOR incr

关 键 词：急性心肌梗死 益气活血方 蛋白激酶B/雷帕霉素靶蛋白信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]