HCV核心蛋白通过LXRα核受体介导HepG2细胞甘油三酯合成增加  

HCV core protein increased the synthesis of triglyceride in HepG2 cells by liver X receptor alpha

作　　者：王晶晶[1] 刘顺爱[2,3] 张锦前[2,3] 全敏[2,3] 冯胜虎[2,3] 王琦[2,3] 赵龙凤[1] 成军[2,3] 

机构地区：[1]山西医科大学第一医院感染病科,太原市030001 [2]首都医科大学附属北京地坛医院传染病研究所 [3]新发突发传染病研究北京市重点实验室

出　　处：《中华实验和临床感染病杂志（电子版）》2014年第1期6-9,共4页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：教育部高等学校博士学科点专项科研基金(No.20121107110012);北京市教委科技计划面上项目(No.11320016)

摘　　要：目的观察丙型肝炎病毒(HCV)的核心蛋白(core)对肝细胞甘油三酯(TG)合成的影响。方法将HCV 1b基因型core表达载体pcDNA3.1-myc/his(-)-core1b和HCV 3a基因型core表达载体pcDNA3.1-myc/his(-)-core3a分别转染至HepG2细胞,利用定量测定法检测细胞内TG含量,用实时荧光定量逆转录聚合酶链反应法(real time qPCR)、蛋白免疫印迹(Western blot)方法观察脂质合成相关基因肝X受体α(LXRα)、甾醇调节元件结合蛋白1c(SREBP1c)和脂肪酸合酶(FASN)的mRNA和蛋白的表达变化,并进行比较分析。结果 HepG2细胞转染两个基因型HCV core表达载体之后均能显著增加细胞内的TG含量(P<0.05),尤以基因型core3a组为差异更显著(P<0.001)。Real-time PCR结果显示,两个基因型core均上调LXRα的mRNA水平(P<0.05),基因型core3a组差异更为显著(P<0.01);FASN的mRNA水平只在仅在基因型core3a组上调(P<0.05),而基因型core1b组差异无统计学意义。Western blot结果显示,HCV core表达可以明显上调表达可以显著上调SREBP1c的蛋白水平,尤其基因型core3a组更为显著。对FASN蛋白水平,基因型core3a上调其表达,但基因型core1b组无明显变化。结论 HCV可能通过LXRα介导肝细胞内的脂质合成诱导肝脂肪变,有待进一步研究。Objective To investigate the effect of HCV core protein on the intracellular triglyceride accumulation in HepG2 cells. Methods HCV core genes were cloned and expressed. Intracellular triglyceride was assessed by quantiifcation with adipogenesis assay kit. The inlfuence of HCV core protein on the liver X receptor （LXRα）, sterol regulatory element binding protein-1c （SREBP1c） and fatty acid synthase （FASN） mRNA expression were analyzed in vitro by real-time PCR. Increased protein expression of SREBP1c and FASN were observed by Western blot. Results There were signiifcant accumulation of triglycerides in both core1b and core3a-expressing HepG2 cells （P＆lt;0.05）, while core3a protein expression induced signiifcant TG accumulation （P＆lt;0.001）. LXRαmRNA expression were upregulated in both cells expressing of HCV core1b （P＆lt;0.05） and core3a （P＆lt;0.01）. FASN mRNA level was increased in core3a-expreession HepG2 cells （P＆lt;0.05）, however, SREBP1c mRNA level was elevated, but with no signiifcant difference. This was accompanied by an increase in protein levels of SREBP1 and FASN. Conclusion LXR alpha-mediated regulation of triglyceride signiifcant by HCV core protein in HepG2 cells.

关 键 词：肝炎病毒 丙型 核心蛋白 肝X受体Α 脂肪变 Liver X receptor (LXRα) 

分 类 号：R512.63[医药卫生—内科学]