五味子乙素通过诱导线粒体自噬减轻心肌缺血再灌注损伤  

Schisandrin B alleviates myocardial ischemia/reperfusion injury via maintaining mitophagy

作　　者：卢长青 贾合磊 雷震 王娟 任冬冬 杨敏华 陈亚奇 Lu Changqing;Jia Helei;Lei Zhen(Dept of Emergency,Henan Province Hospital of TCM (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine),Zhengzhou 450002)

机构地区：[1]河南省中医院(河南中医药大学第二附属医院)急诊科,郑州450002

出　　处：《安徽医科大学学报》2019年第3期418-422,428,共6页Acta Universitatis Medicinalis Anhui

基　　金：河南省科技攻关计划项目(编号:112102310198)

摘　　要：目的探究五味子乙素(Sch B)对心肌缺血再灌注(MI/R)损伤的作用及其机制。方法将小鼠随机分为对照(Sham)组、Sham+Sch B组、MI/R model组和MI/R model+Sch B组; MI/R model组和MI/R model+Sch B组采用冠状动脉结扎法复制小鼠MI/R模型,Sham+Sch B组和MI/R model+Sch B组给予Sch B (80 mg/kg/d),记录小鼠心率,30 d后处死小鼠,试剂盒检测血清乳酸盐脱氢酶(LDH)和肌酸激酶CK)的含量; HE染色检测心肌组织病理情况;qRT-PCR和Western blot法检测线粒体自噬相关分子mRNA水平和蛋白表达水平; Western blot检测腺苷酸活化蛋白激酶(AMPK)/雷帕霉素靶蛋白mT OR)/ULK1通路标记蛋白的表达。腺苷酸活化蛋白激酶-β1基因敲除(AMPK-β1-/-)小鼠重复上述实验。结果 Sch B能显著降低MI/R小鼠心肌损伤指标(血清LDH和CK的含量、心肌梗死面积)、加快MI/R小鼠心率,并改善MI/R小鼠心肌病理损伤;同时,Sch B能显著升高线粒体自噬标记蛋白环氧化酶I (COXI)和COX IV的mRNA水平和缺氧诱导因子-1α(HIF-1α)和Beclin1蛋白表达水平; Sch B还可显著促进p-AMPK和pULK1的表达,抑制p-mTOR的表达。AMPK-β1-/-小鼠线粒体自噬明显被抑制,导致心肌梗死面积明显增大,心率显著降低。结论 Sch B可通过诱导线粒体自噬减轻小鼠心肌缺血再灌注损伤。Objective To investigate the effects and mechanism of schisandrin B(Sch B)on myocardial ischemia/reperfusion(MI/R)injury.Methods Mice were divided into Sham,Sham+Sch B,MI/R model and MI/R model+Sch B groups.Replication of mouse MI/R model by coronary artery ligation and mice in Sham+Sch B and MI/R model+Sch B group were treated with Sch B,and recorded the heart rate at the same time.Mice were sacrificed after administering with Sch B for 30 days.The serum lactate dehydrogenase(LDH)and creatine kinase(CK)were detected by reagent cases,and pathologic lesions were measured by HE staining.The mRNA and protein levels of mitophagy related proteins were calculated by qRT-PCR and Western blot.Adenosine monophosphate activated protein kinase/mammalian target of rapamycin/ULK1(AMPK/mTOR/ULK1)pathway related proteins also were detected by Western blot.The above-mentioned tests were repeated by using AMPK-β1 gene konockout(AMPK-β1-/-)mice.Results Sch B treatment decreased the indexes of cardiac injury(serum LDH,CK and the myocardial infract area),increased the heart rate and alleviated the pathological changes.Meanwhile,Sch B maintained mitophagy by up-regulating the mRNA levels of cyclooxygenase I(COX I),COX IV and increasing protein levels of hypoxia-inducible factor-1α(HIF-1α),Beclin 1.In addition,Sch B increased the expression of p-AMPK,p-ULK1 and decreased the expression of p-mTOR induced by MI/R injury.Furthermore,knockout AMPK-β1 inhibited mitophagy,thus resulted in the increasing infract area and decreasing heart rate.Conclusion Sch B alleviates MI/R injury via maintaining mitophagy mediated by AMPK/mTOR/ULK1 signaling pathway.

关 键 词：五味子乙素 缺血再灌注 线粒体自噬 

分 类 号：R542.2[医药卫生—心血管疾病]