阿托伐他汀通过内质网应激调节乙醇作用下AC16心肌细胞超微结构及脂质合成代谢  

Effects of Atorvastatin on Ultrastructure and Lipid Synthesis of Myocardial AC16 Cells Exposed to Alcohol through Endoplasmic Reticulum Stress

作　　者：李宁[1] 张航 于波[1] LI Ning;ZHANG Hang;YU Bo(Department of Cardiology,The First Hospital,China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院心内科

出　　处：《中国医科大学学报》2019年第9期828-832,共5页Journal of China Medical University

基　　金：沈阳市科技计划(F16-206-9-08,F17-230-9-59)

摘　　要：目的探讨阿托伐他汀通过内质网应激(ERS)对乙醇作用下AC16心肌细胞超微结构及脂质合成代谢的影响及机制。方法建立乙醇作用下AC16心肌细胞ERS模型,并通过Western blotting检测葡萄糖调节蛋白78(GRP78)的表达,确认ERS模型建立成功。使用不同浓度(1、10、100μmol/L)阿托伐他汀处理乙醇作用下AC16心肌细胞,采用Western blotting检测GRP78蛋白的表达,电镜观察心肌细胞超微结构,检测脂质合成代谢关键蛋白固醇调节原件结合蛋白-1c(SREBP-1c)、甘油三酯含量变化。结果成功建立乙醇作用下AC16心肌细胞ERS模型。相对于乙醇组,1、10、100μmol/L阿托伐他汀组GRP78、SREBP-1c和甘油三酯含量均显著降低。乙醇组细胞形态异常、细胞内线粒体数量明显减少、线粒体增大、线粒体嵴结构紊乱,随着阿托伐他汀干预浓度增加,细胞形态及线粒体结构逐渐趋于正常,其中100μmol/L阿托伐他汀组可见大量线粒体,呈椭圆形,线粒体嵴结构整齐,同正常组。结论阿托伐他汀可抑制乙醇作用下ERS相关因子GRP78的表达,改善酒精性心肌病细胞模型细胞体态、线粒体等超微结构及脂代谢情况。Objective To investigate the effects of atorvastatin on the ultrastructure of and lipid synthesis and its mechanism of action in myocardial AC16 cells under endoplasmic reticulum stress(ERS)induced via alcohol exposure.Methods We established the ERS model in myocardial AC16 cells exposed to alcohol and verified the establishment of the ERS model by examining GRP78 expression using Western blotting.AC16 cells were treated with different concentrations(1,10,and 100μmol/L)of atorvastatin after administration of al-cohol.Expression of the GRP78 protein was detected using Western blotting,ultrastructure of the AC16 cells was observed using electron microscopy,and the contents of sterol regulatory element binding protein-1c(SREBP-1c)and triglycerides were detected.Results The ERS model was successfully established in AC16 cells by exposure to alcohol.Compared with the alcohol administered group,the levels of GRP78,SREBP-1c,and triglycerides in groups treated with 1,10,and 100μmol/L atorvastatin were reduced significantly.In alcohol ad-ministered group,the cell morphology and mitochondrial structure were abnormal,the number of mitochondria was reduced,the mitochon-dria enlarged,and the mitochondrial ridge structure was disordered.With the increase in atorvastatin concentration,cell morphology and mitochondrial structure gradually became characteristically healthy.A large number of mitochondria were found in the 100μmol/L ator-vastatin treated group;they were oval in shape,and the mitochondrial ridge structure was similar to that in the normal group.Conclusion Atorvastatin can inhibit expression of the ERS related factor,GRP78,improve cellular morphology and ultrastructure and lipid metabolism in myocardial AC16 cells exposed to alcohol.

关 键 词：阿托伐他汀 内质网应激 心肌细胞AC16 超微结构 脂质合成代谢 

分 类 号：R541.9[医药卫生—心血管疾病]