TSPAN8参与小鼠非酒精性脂肪性肝病的脂质代谢  

TSPAN8 is involved in lipid metabolism in non-alcoholic fatty liver disease in mice

作　　者：张佳 薛薇 章述军[1] 朱雅莉 阳成[1] 高月 石凌枫 黄文祥[1] ZHANG Jia;XUE Wei;ZHANG Shujun;ZHU Yali;YANG Cheng;GAO Yue;SHI Lingfeng;HUANG Wenxiang(Department of Infectious Diseases,First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院感染科,重庆400016

出　　处：《南方医科大学学报》2022年第5期705-711,共7页Journal of Southern Medical University

基　　金：重庆市渝中区基础研究与前沿探索项目(203011320190012);重庆市科委基础科学与前沿技术研究重点项目(csct2015jcyjBX0097)。

摘　　要：目的探讨四跨膜蛋白8(TSPAN8)在非酒精性脂肪性肝病(NAFLD)发生发展中的变化及其在脂质代谢中的作用。方法将30只C57BL/6J雄性小鼠随机分为普通饲料组(ND,n=15)和高脂饲料组(HFD,n=15)。Westernblot检测1、3、6月末各组小鼠肝脏组织中TSPAN8的表达水平。HepG2细胞分成6组:完全培养基培养,无其他处理的命名为对照组(CON);游离脂肪酸(FFA)处理以构建NAFLD细胞模型的命名为FFA组;TSPAN8过表达细胞命名为PCDNA-TSPAN8组,其对照为PCDNA3.1组;FFA处理后的PCDNA-TSPAN8命名为PCDNA-TSPAN8+FFA组,其对照为PCDNA3.1+FFA组;qRT-PCR及Westernblot检测CON组和FFA组细胞中TSPAN8表达水平;油红O染色法和全自动生化仪检测PCDNA-TSPAN8+FFA和PCDNA3.1+FFA组细胞内脂质蓄积情况。qRT-PCR检测与脂质代谢相关基因mRNA的表达情况。结果Westernblot显示,与同喂养时间ND组相比,HFD喂养3、6月的小鼠肝组织中TSPAN8的表达下降(P<0.05)。qRT-PCR与Westernblot显示,与CON组比较,TSPAN8在FFA组中的表达下降(P<0.01)。与PCDNA3.1+FFA组相比,PCDNA-TSPAN8+FFA组中细胞内甘油三酯(TG)水平下降(P<0.001)。qRT-PCR示,与PCDNA3.1组比较,脂肪酸转运蛋白5(FATP5)在PCDNA-TSPAN8组中表达降低(P<0.01),与CON组相比,FATP5在FFA组表达上调(P<0.001)。结论TSPAN8参与NAFLD的脂质代谢,细胞过表达TSPAN8可能通过降低FATP5的表达来抑制细胞内脂质的沉积,可能具有潜在的临床价值。Objective To investigate the changes of tetraspanin 8(TSPAN8)expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease(NAFLD).Methods Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=15),and after feeding for 1,3,and 6 months,the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting.In a HepG2 cell model of NAFLD induced by free fatty acids(FFA),the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer,and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.Results Western blotting showed that compared with that in mice with normal feeding,the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months(P<0.05).In HepG2 cells,treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels(P<0.01).TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels(P<0.001)and obviously reduced mRNA expression of fatty acid transport protein 5(FATP5)(P<0.01).The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells(P<0.001).Conclusion TSPAN8 is involved in lipid metabolism in NAFLD,and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.

关 键 词：非酒精性脂肪性肝病 四跨膜蛋白8 脂代谢 

分 类 号：R575.5[医药卫生—消化系统]