关键词: 丙型肝炎病毒, 核心蛋白, 沉默信息调节因子1,SIRT1, 脂联素, 脂滴自噬

Abstract: Objective To investigate the effect of lipophagy on hepatitis C virus (HCV) core protein-induced hepatic steatosis via down-regulating silent information regulator 1 (SIRT1) in mice.Methods Mice were randomized into HCV group and control group (n=10 in both groups), with injection of HCV core recombinant expression vectors or sterile phosphate buffered solution (PBS) through the tail vein, respectively. All mice were sacrificed in 1 month after the injection. Liver function and serum adiponectin were collected. Total triacylglycerol (TG) were measured in both serum and liver tissues. Levels of SIRT1 protein, adiponectin receptor 2 (AdipoR2) protein, light chain 3-Ⅱ (LC3-Ⅱ) protein, adipose differentiation related protein (ADRP), tail interacting protein 47KD (TIP-47) and P62 protein in liver were measured using western blot. Quantitative data was analyzed using t-test.Results In HCV group, histopathological examinations revealed hepatic steatosis, and the hepatic TG content ( 80.9±20.1 vs 45.8±10.5 μg/mg, t=4.964, P<0.01) and levels of LC3-Ⅱ protein (0.8±0.2 vs 0.4±0.1, t=5.656, P<0.01), TIP-47 protein (0.9±0.3 vs 0.4±0.1, t=5.000, P<0.01) and ADRP protein (0.8±0.3 vs 0.4±0.1, t=4.000, P<0.01) were all increased than those in the control group. However, serum adiponectin (1.05±0.25 vs 1.41±0.45 ng/ml, t=2.211, P<0.05 ), SIRT1 protein (0.4±0.1 vs 0.9±0.2, t=7.071, P<0.01) and AdipoR2 protein (0.4±0.1 vs 0.8±0.2, t=5.656, P<0.01) were decreased in HCV mice group compared with those in control group. Expression of P62 protein (0.7±0.2 vs 0.8±0.3, t=0.877, P>0.05) showed no significant difference between the two groups.Conclusion HCV core protein might cause hepatic steatosis via inducing incomplete lipophagy through down-regulating the expression of SIRT1, adiponectin and AdipoR2.

Key words: Hepatitis C virus, Core protein, Silent information regulator 1, Adiponectin, Lipophagy