摘要
目的:探讨过氧化物酶体增殖物激活受体γ(PPARγ)对巨噬细胞胆固醇外流的影响。方法 :建立高脂、急性炎症等不同病理状态的C57BL/6小鼠模型并分离培养其腹腔巨噬细胞,观察细胞PPARγ与IκB-α表达变化;采用PPARγ激动剂ciglitazone和PPARγ反义寡核苷酸预处理正常腹腔巨噬细胞,体外观察内毒素刺激对细胞胆固醇外流的影响。结果:高脂组和LPS组PPARγ蛋白表达较正常对照组均明显增高(P<0.05),高脂组IκB-α表达较正常组轻度降低,两种饮食经LPS刺激后IκB-α表达较正常组均显著降低(P<0.01)。胆固醇外流测定结果显示,高脂组细胞胆固醇外流较正常组明显增强(P<0.05),高脂及正常饮食组经LPS刺激后较正常对照组均明显减弱(P<0.05)。PPARγ激动剂预处理腹腔巨噬细胞,LPS刺激后PPARγ蛋白表达较正常对照组升高(P<0.05),IκB-α蛋白表达低于正常组(P>0.05)。PPARγ反义寡核苷酸预处理亦可导致巨噬细胞胆固醇外流受到抑制,但抑制程度高于正常对照组。结论:PPARγ激动剂可增强巨噬细胞胆固醇外流,而抑制PPARγ的表达则抑制C57小鼠腹腔巨噬细胞胆固醇外流。
Objective:To explore the effects of PPARγon the cholesterol efflux of C57 mice peritoneal macrophage.Methods:Firstly constructing C57 mice model under different metabolic situation including high-fat diet and acute inflammation then isolate and culture its peritoneal macrophage,observing the expressions of PPARγand IκB-α,identify the character of macrophage cholesterol efflux in every group.Then pretreat the normol C57 mice peritoneal macrophage with PPARγligand ciglitazone and PPARγantisense oligonucleotide,observing the effect to cholesterol efflux after simulated with LPS in vitro.Results:The level of mice serumlipids of high fat diet group was significantly higher than that of normal diet group.The results of Western-blotting showed that the expression of PPARγprotein in groups of HFD and stimulated by LPS were significantly higher than that of control group.The expression in groups stimulated by LPS was all lower significantly than in control grouph.The determination of cholesterol efflux showed that this function of macrophage with HFD was more enhanced than that of control group but was inhibited in group stimulated by LPS.To normol peritoneal macrophage pretreat with PPARγantisense oligonucleotide and stimulated by LPS,the expression of PPARγprotein was lower than that of control group but the expression of IκB-αwas depressed obviously.Conclusion:The PPARγligand ciglitazone can increase the cholesterol efflux of C57 mice peritoneal macrophage and weaken the inhibition stimulated by LPS.The PPARγantisense oligonucleotide can depress it and aggravate the inhibition.
作者
游海波
何堃
李钺
龚建平
李旭宏
YOU Hai-bo;HE Kun;LI Yue;GONG Jian-ping;LI Xu-hong(Department of General Surgery,The Peopled Hospital in Changshou District of ChongqingfChongqing 401220,China;department of Hepatobiliary Surgery,The Second AtSliated Hospital,Chongqing Medical University Chongqing,400010,China)
出处
《中国现代普通外科进展》
CAS
2017年第11期851-855,共5页
Chinese Journal of Current Advances in General Surgery
基金
重庆市卫生计生委医学科研计划项目(2015MSXM123)
重庆市自然科学基金(CSTCjj A10013)
