脂多糖通过自噬作用促进氧化低密度脂蛋白诱导的泡沫细胞的形成  

Lipopolysaccharide Enhances ox-LDL-induced Foam Cell Formation through Autophagy

作　　者：袁媛[1] 张利军[2] 王超[1] 郑鹏飞[3] 张秀敏[1] 叶菁[1] 冯旭阳[3] 

机构地区：[1]第四军医大学病理学与病理生理学教研室,陕西西安710032 [2]唐都医院实验与检验输血科,陕西西安710032 [3]西京医院心脏内科,陕西西安710032

出　　处：《现代生物医学进展》2014年第12期2205-2209,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81070248;81070249);陕西省自然科学基础研究计划项目(2013JQ4020)

摘　　要：目的:研究脂多糖(LPS)促进氧化低密度脂蛋白(ox-LDL)诱导的泡沫细胞形成的机制。方法:人源性THP-1细胞的培养,经ox-LDL诱导形成泡沫细胞。采用油红O染色鉴定泡沫细胞的形成,免疫荧光和Western blot方法检测自噬活性,观察自噬作用对泡沫细胞脂质沉积的影响。结果:①经形态学观察,脂多糖可以促进ox-LDL诱导的泡沫细胞的形成。②脂多糖可以激活自噬作用,并且自噬活性在16h达到最强。③脂多糖可以增强自噬激活剂雷帕霉素(Rap)的促自噬作用(P<0.05),并且削弱自噬抑制剂3-甲基腺嘌呤(3-MA)的作用。④Rap单独作用不能影响泡沫细胞中脂质的累积,然而脂多糖能够增强Rap的作用,显著促进脂滴在泡沫细胞中的累积(P<0.05);3-MA可以抑制基础水平和脂多糖诱导后泡沫细胞中脂滴的积累。结论:脂多糖通过增强自噬作用促进泡沫细胞的形成。Objective：To investigate the mechanism of LPS in the ox-LDL-induced foam cell formation.Methods：Human THP-1 cells were cultured and differentiated into foam cells by the addition of ox-LDL.The foam cell formation was evaluated by Oil red O staining.The autophagic activity was determined by immunofluorescence and Western blot analysis.Results：① By observing the morphology of the foam cells,it was found LPS enhanced ox-LDL induced lipid accumulation during the foam cell formation.②LPS induced autophagy in human macrophages-derived foam cell formation.Moreover,the time-course（0h,8h,16h,or 24h） experiments revealed that the percentage of cells expressing autophagosomes was maximal at 16hr after LPS stimulation.③ Autophagic activity in human THP-1 macrophages was either stimulated with Rap or inhibited by 3-MA.LPS could augment the activity of autophagy after Rap and prevent the role of 3-MA.④ Lipid accumulation increased by the exposure to LPS,and the increase was enhanced by Rap.In contrast,inhibition of autophagy with 3-MA prevented both the basal and the LPS-induced lipid accumulation.Rapalone did not alter the level of total cholesterol or triglyceride,while inhibition of autophagy with 3-MA decreased triglyceride in macrophages either treated with LPS or not（P0.05）.Conclusion：LPS augments the foam cell formation through autophagy.

关 键 词：脂多糖 自噬 泡沫细胞 OX-LDL 

分 类 号：Q813[生物学—生物工程] R543.5[医药卫生—心血管疾病]