香青兰总黄酮对心肌缺血再灌注损伤大鼠mTOR信号通路及相关自噬蛋白水平的影响  

Effects of Dracocephalum Moldavica L.total flavonoids on mTOR signaling pathway and related autophagy protein levels in rats with myocardial ischemia-reperfusion injury

作　　者：梁自强 邓洁 袁勇[2] 马晓莉 郭新红[2] 黄川生[2] 曹文疆[2] LIANG Ziqiang;DENG Jie;YUAN Yong;MA Xiaoli;GUO Xinhong;HUANG Chuansheng;CAO Wenjiang(Pharmacy of College,Shihezi University,Shihezi,Xinjiang 832002,China;First Affiliated Hospital of the Medical College,Shihezi University,Shihezi,Xinjiang 832008,China)

机构地区：[1]石河子大学药学院,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832008

出　　处：《石河子大学学报（自然科学版）》2020年第4期513-518,共6页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81660704、81960766)。

摘　　要：目的研究香青兰总黄酮调控AMPK/mTOR和PI3K/AKT/mTOR信号通路抗心肌缺血再灌注损伤(MIRI)的药效学机制。方法结扎大鼠冠状动脉左前降支缺血30 min,再灌注2 h构建MIRI模型;TTC染色法测定心肌梗死面积;HE染色法测定心肌病理学形态;蛋白免疫印迹法检测LC3、Beclin1、Bcl-2、mTOR、p-mTOR、AMPK、p-AMPK、AKT和p-AKT蛋白表达。结果与模型组相比,香青兰总黄酮可以减轻心肌梗死面积(P<0.001),改善心肌病理学形态,下调LC3和Beclin1的蛋白水平(P<0.05或P<0.01),上调Bcl-2、p-mTOR、p-AMPK和p-AKT的蛋白水平(P<0.05或P<0.01)。但香青兰总黄酮分别联用mTOR抑制剂Rapamycin、AMPK抑制剂Compound C和PI3K抑制剂LY294002之后,香青兰总黄酮的保护作用消失了。结论香青兰总黄酮具有抗心肌缺血再灌注损伤的保护作用,其机制可能与AMPK/mTOR和PI3K/AKT/mTOR信号通路有关。Objective To study the pharmacodynamic mechanism of Dracocephalum Moldavica L.total flavonoids regulating AMPK/mTOR and PI3K/AKT/mTOR signaling pathway against myocardial ischemia-reperfusion injury.Methods The MIRI model was established by 30 min of coronary occlusion followed by 2 h of reperfusion in rats;the area of myocardial infarction was determined by TTC staining;the pathological morphology of myocardium was determined by HE staining;LC3,Beclin1,Bcl-2,mTOR,p-mTOR,AMPK,p-AMPK,AKT and p-AKT proteins expression was investigated by Western Blot.Results Compared with the model group,Dracocephalum Moldavica L.total flavonoids can reduce the area of myocardial infarction(P<0.001),improve the myocardial pathological morphology,down-regulate the protein levels of LC3 and Beclin1(P<0.05 or P<0.01),and up-regulate Bcl-2,p-mTOR,p-AMPK and p-AKT protein levels(P<0.05 or P<0.01).However,After Dracocephalum Moldavica L.total flavonoids combined mTOR inhibitor Rapamycin,AMPK inhibitor Compound C and PI3K inhibitor LY294002,the protective effect of Dracocephalum Moldavica L.total flavonoids disappeared.Conclusion Dracocephalum Moldavica L.total flavonoids have protective effects on myocardial ischemia-reperfusion injury,and its mechanism may be related to the AMPK/mTOR and PI3K/AKT/mTOR signaling pathways.

关 键 词：香青兰总黄酮 自噬 AMPK AKT MTOR 

分 类 号：R285.5[医药卫生—中药学]