γ疱疹病毒68病毒感染对小鼠肝脏脂质积聚的影响

Effects of murine gamma herpesvirus 68 infection on hepatic lipid accumulation of C57BL/6J mice

目的:观察鼠γ疱疹病毒68感染对C57BL/5J小鼠肝脏脂质积聚的影响并探讨其潜在机制。方法:采用高脂饮食喂养C57BL/6J小鼠,并用腹腔注射病毒的方法感染小鼠,处理18周后,检测血清炎症因子含量和肝脏组织炎症因子的表达,对小鼠肝脏进行HE和油红O染色,并用荧光定量逆转录PCR和Western blot检测脂肪酸代谢途径中关键基因的mRNA和蛋白表达。结果:与单纯高脂饮食喂养的小鼠比较,病毒感染小鼠的血清白介素6和血清淀粉样蛋白A含量增加(t值分别为-3.285和-6.528,P值分别为0.008和0.000),肝脏肿瘤坏死因子表达水平也升高(t=-5.234,P=0.002),肝脏组织的脂肪变性程度加重,肝脏内甘油三酯和游离脂肪酸的含量明显高于对照组(t值分别为-3.440和-2.967,P值分别为0.006和0.020)。同时病毒感染促进了小鼠肝脏的固醇调节元件结合蛋白1,脂肪酸合成酶和乙酰辅酶A羧化酶的mRNA表达水平(t值分别为-4.659,-4.210和-4.521,P值分别为0.001、0.004和0.004)和蛋白表达。结论:腹腔注射疱疹病毒能成功感染C57BL/6J小鼠,引起小鼠全身系统性和肝脏局部的炎症反应,促进脂质在肝脏的异常积聚,这可能与炎症状态下脂肪酸合成与羧化的关键基因表达异常增加有关。

Objective：To investigate the effects of murine gamma herpesvirus 68（γHV68） infection on lipid accumulation in the liver of C57BL/6J mice and to explore the potential mechanisms.Methods：C57BL/6J mice fed with high fat diet were randomly assigned to receive either γHV68 or phosphate buffer treatment.Serum was analyzed for inflammatory cytokines.Liver was taken for histology and lipid analysis by HE and oil red O staining.Fluorescence quantitative RT-PCR and Western blot were used to measure expressions of hepatic tumor necrosis factor-α（TNF-α）,sterol regulatory element binding protein-1（SREBP1）,fatty acid synthase（FAS）,acetyl CoA carboxylase（ACC）.Results：γHV68 infection promoted lipid accumulation in the liver of C57BL/6J mice in association with elevated serum interleukin 6 and serum amyloid A protein levels（t=-3.285,-6.528;P=0.008,0.000） as well as the elevated TNF-α expressions（t=-5.234,P=0.002）.Degree of hepatic steatosis was increased after infection;concentrations of triglyceride and free fatty acid in the liver were obviously higher in γHV68-infected mice than in control mice（t=-3.440,-2.967;P=0.006,0.020）.mRNA and protein expressions of SREBP1,FAS and ACC in the liver were increased in γHV68-infected mice than in control mice（t=-4.659,-4.210 and-4.521;P=0.001,0.004 and 0.004）.Conclusions：Intraperitoneal injection of herpes virus can successfully infect C57BL/6 mice and induce systemic and local liver inflammatory reaction of mice.γHV68 infection promotes liver lipid accumulation in C57BL/6J mice,which possibly correlates with increased fatty acid synthesis and expressions of key genes of carboxylation.