依泽替米贝对非酒精性脂肪肝病细胞模型脂质沉积和凋亡的影响及其与自噬关系的研究  

Effects of Ezetimibe on Lipid Deposition and Apoptosis in Nonalcoholic Fatty Liver Disease Cell Model and Its Relationship with Autophagy

作　　者：宋琪 吴鹏波[1] 谭诗云[1] SONG Qi;WU Pengbo;TAN Shiyun(Department of Gastroenterology,Renmin Hospital of Wuhan University/Hubei Key Laboratory of Digestive System Disease,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院消化内科消化系统疾病湖北省重点实验室,武汉430060

出　　处：《医学综述》2019年第8期1650-1655,共6页Medical Recapitulate

基　　金：湖北省卫生计生委面上项目(WJ2017M019)

摘　　要：目的探讨依泽替米贝(Eze)对以油酸(OA)预处理Hep G2细胞为模型的非酒精性脂肪肝病(NAFLD)细胞模型脂质沉积和凋亡的影响及其与自噬的关系。方法以OA预处理Hep G2细胞为NAFLD细胞模型,加入Eze及自噬抑制剂氯喹(CQ)干预其过程;通过油红O染色检测Eze对肝细胞内脂质沉积的影响;细胞计数试剂盒8和流式细胞术检测Eze对肝细胞增殖和凋亡的影响; Western blot及免疫荧光染色检测Eze对肝细胞Beclin-1和微管相关蛋白1轻链3(LC3)表达水平的影响。结果经Eze处理后,OA预处理的Hep G2细胞增殖活性无明显改变(P> 0. 05); OA+Eze组细胞脂质沉积少于OA组,OA诱导的细胞凋亡率低于OA组[(2. 777±0. 114)%比(1. 673±0. 094)%](P <0. 01),Beclin-1和LC3蛋白表达高于OA组(1. 101±0. 099比0. 738±0. 079、1. 948±0. 318比1. 196±0. 060)(P <0. 05);加入CQ后,OA+Eze+CQ组细胞脂质沉积多于OA+Eze组,细胞凋亡率和LC3蛋白表达水平高于OA+Eze组[(5. 710±0. 109)%比(1. 673±0. 094)%、(4. 326±1. 361)比(1. 948±0. 318)](P <0. 05),Beclin-1表达水平低于OA+Eze组(0. 603±0. 108比1. 101±0. 099)(P <0. 05)。结论 Eze可降低NAFLD细胞模型中细胞内脂质沉积和细胞凋亡率,因此可能对NAFLD具有一定的治疗作用,其作用机制可能是通过增强非酒精性脂肪肝细胞的自噬水平实现的。Objective To investigate effects of ezetimibe(Eze) on lipid deposition and apoptosis in oleic acid(OA) induced nonalcoholic fatty liver disease(NAFLD) HepG2 cell model and its relationship with autophagy. Methods HepG2 cells were pretreated with OA to establish a NAFLD cell model.Eze and autophagy inhibitor chloroquine(CQ) were added to interfere with the process.The effect of Eze on lipid deposition in HepG2 cells was detected by oil red O staining,and proliferation rate by cell counting Kit-8,apoptosis rate by flow cytometry,expression levels of Beclin-1 and microtubule associated protein1 light-chain3(LC3) proteins by Western blotting and immunofluorescence staining. Results After addition of Eze,the proliferative activity of OA-pretreated HepG2 cells did not change significantly( P >0.05).The lipid deposition of the OA+Eze group was less than that of the OA group,and OA-induced apoptosis in the OA+Eze group were lower than those in the OA group[(2.777±0.114)% vs (1.673±0.094)%]( P < 0.01),but the expression levels of Beclin -1 and LC3 proteins were higher(1.101±0.099 vs 0.738±0.079,1.948±0.318 vs1.196±0.060)( P <0.05).After adding CQ,lipid deposition of the OA+EZe+CQ group was more than that of the OA+Eze group,apoptosis rate and the expression level of LC3 in the OA+Eze+CQ group were higher than those in the OA+Eze group[(5.710±0.109)% vs (1.673±0.094)%,(4.326±1.361) vs (1.948±0.318)]( P <0.05), but the expression level of Beclin-1 was lower (0.603±0.108 vs 1.101±0.099)( P <0.05). Conclusion Eze may have a therapeutic effect on NAFLD since it can reduce intracellular lipid deposition and apoptosis rate in NAFLD cell model,and the mechanism may be enhancing autophagy level in nonalcoholic fatty liver cells.

关 键 词：非酒精性脂肪肝病 依泽替米贝 自噬 

分 类 号：R575.5[医药卫生—消化系统]