γHV68病毒感染对小鼠肝脏脂质积聚的影响

The effects of γHV68 infection on C57BL/6J mice liver steatosis

摘要:

目的：观察鼠γ疱疹病毒(γHV68)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,肝脏肿瘤坏死因子表达水平也升高,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。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。

Abstract:

Objective: To investigate the effect of murine gamma herpesvirus 68 (γHV68) infection on lipid accumulation in livers of C57BL/6J mice and to explore potential mechanisms. Methods: C57BL/6J mice fed a high fat diet were randomly assigned to receive either γHV68 or PBS treatment. Serum was analyzed for inflammatory cytokines. Liver was taken for histology and lipid analysis. Quantitative RT-PCR was used to measure expression of hepatic tumor necrosis factor alpha (TNFα), sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC). Results: γHV68 infection promoted lipid accumulation in livers of C57BL/6J mice in association with elevated serum and hepatic inflammatory cytokines levels. The expression of SREBP1, FAS and ACC in livers of C57BL/6J mice were increased in the γHV68-infected mice. Conclusion: γHV68 infection promotes liver lipid accumulation in C57BL/6J mice via increasing triglyceride synthesis.