摘要
目的通过动物实验探究Akt/mTOR信号介导的自噬在盐酸小檗碱(BBR)治疗小鼠心肌梗死损伤中的作用。方法将40只8周龄C57BL/6小鼠随机分为假手术组(Sham组)、单纯BBR处理组(BBR组)、心肌梗死组(MI组)和BBR干预心肌梗死组(BBR+MI组),每组10只。采用冠状动脉左前降支结扎术制备心肌梗死小鼠模型,BBR组和BBR+MI组手术后给予20 mg/(kg·d)BBR灌胃28 d。HE染色观察心肌组织形态学变化,检测血清乳酸脱氢酶(LDH)的含量,TUNEL染色检测细胞凋亡情况,Western blot检测自噬相关蛋白p62、Beclin1和Akt/mTOR通路蛋白磷酸化的表达。结果与Sham组比较,MI组心肌纤维断裂明显,排列紊乱,TUNEL阳性细胞核染色数量增多;血清LDH含量和心肌细胞凋亡率升高(P<0.01);p-Akt、p-mTOR和Beclin1表达升高,而p62表达降低(P<0.01)。与MI组比较,BBR+MI组心肌纤维的断裂明显减轻,TUNEL阳性细胞核染色数量明显减少;血清LDH含量和心肌细胞凋亡率降低(P<0.01);p-Akt、p-mTOR和Beclin1表达量降低,而p62表达升高(P<0.01)。结论BBR能通过Akt/mTOR信号调节自噬从而减轻小鼠心肌梗死损伤。
Objective To investigate effect of Akt/mTOR signal-mediated autophagy in mice with myocardial infarction injury treated by Berberine Hydrochloride(BBR).Methods A total of 408-week-old C57BL/6 mice were randomly divided into sham operated group(n=10,Sham group),only BBR treatment group(n=10,BBR group),myocardial infarction group(n=10,MI group)and BBR intervention myocardial infarction group(n=10,BBR+MI group).Mice models of myocardial infarction were made by using ligation of left anterior descending coronary artery.Mice in BBR and BBR+MI groups were lavaged with 20 mg/(kg·d)BBR for 28 d after operation.Hematoxylin and eosin(HE)staining was used to observe changes of myocardial histomorphology and serum lactate dehydrogenase(LDH)content.TUNEL staining was used to detect apoptosis condition.Expressions of autophagy related proteins p62,Beclin1 and Akt/mTOR pathway proteins phosphorylation were detected by Western blot.Results Compared with those in Sham group,in MI group,myocardial fibers were obviously broken and disordered in rank,and number of TUNEL positive nuclear staining was increased,and serum LDH content and apoptosis rate of cardiomyocytes were increased(P<0.01),expressions of p-Akt,p-mTOR and Beclin1 were increased,while p62 expression was decreased(P<0.01).Compared with those in MI group,in BBR+MI group,breakage of myocardial fiber was significantly decreased,and number of TUNEL positive nuclear staining was decreased,and serum LDH content and apoptosis rate of cardiomyocyte were decreased(P<0.01);expressions of p-Akt,p-mTOR and Beclin1 were decreased,while p62 expression was increased(P<0.01).Conclusion BBR may regulate autophagy through Akt/mTOR signal to decrease myocardial infarction injury in mice.
作者
田磊
金屏
贺清
吕珊珊
郑云
冯波
闫晓丽
TIAN Lei;JIN Ping;HE Qing;LYU Shan-shan;ZHENG Yun;FENG Bo;YAN Xiao-li(Department of Cardiothoracic Surgery,the Third Hospital of Xi'an,Xi'an 710018,China;Department of Cardiovascular Surgery,Xijing Hospital Affiliated to Military Medical University of PLA Air Force,Xi'an 710032,China)
出处
《解放军医药杂志》
CAS
2019年第12期1-5,共5页
Medical & Pharmaceutical Journal of Chinese People’s Liberation Army
基金
国家自然科学基金项目(81774415)
国家重点研发计划(2016YFC1101000)
西京医院学科助推计划(XJZT15ZL01)
