HCV对脂代谢相关指标表达的影响

Influence of hepatitis C virus on the expression of lipid metabolism indices

目的研究HCV在体内外对脂代谢相关指标表达的影响。方法选取武汉大学人民医院2017年10月-2018年10月HCV感染者的标本114例(试验组)和健康体检者标本96例(对照组),采用全自动生化分析仪检测血脂指标,包括甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、小而低密度脂蛋白、脂蛋白a、载脂蛋白A1和载脂蛋白B的血清水平;采用实时荧光定量PCR检测HCV感染的Huh7. 5. 1细胞(实验细胞)和未感染HCV的Huh7. 5. 1细胞(对照细胞)中脂肪酸合成酶、乙酰CoA羧化酶、羟甲基戊二酸单酰CoA还原酶、载脂蛋白A1、载脂蛋白B和低密度脂蛋白受体mRNA的表达量。正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验。结果试验组患者血清总胆固醇、高密度脂蛋白、低密度脂蛋白、载脂蛋白A1和载脂蛋白B水平均低于对照组[分别为(2. 98±0. 51) mmol/L vs (4. 24±0. 43) mmol/L、(0. 87±0. 16) mmol/L vs (1. 24±0. 21) mmol/L、(1. 75±0. 24) mmol/L vs (2. 64±0. 37) mmol/L、(0. 94±0. 18) mmol/L vs (1. 47±0. 26) mmol/L、(0. 67±0. 31) mmol/L vs (0. 98±0. 14) mmol/L],差异均有统计学意义(t值分别为4. 96、5. 65、3. 88、3. 71、4. 41,P值均<0. 05)。实验细胞中载脂蛋白A1 mRNA表达水平较对照细胞低,差异有统计学意义(t=-3. 43,P <0. 05);脂肪酸合成酶、乙酰CoA羧化酶、羟甲基戊二酸单酰CoA还原酶、载脂蛋白B和低密度脂蛋白受体的mRNA表达水平均较对照细胞高,差异均有统计学意义(t值分别为5. 40、4. 93、3. 34、6. 88、3. 84,P值均<0. 05)。结论 HCV感染能够上调肝细胞内脂肪酸和胆固醇合成相关酶类基因mRNA水平,在体内和体外影响机体脂代谢。

Objective To investigate the influence of hepatitis C virus (HCV) on the expression of lipid metabolism indices in vitro and in vivo. Methods A total of 114 samples of patients with HCV infection who were treated in Renmin Hospital of Wuhan University from September 2017 to September 2018 were collected as experimental group,and 96 samples of healthy individuals who underwent physical examination were collected as control group. An automatic biochemical analyzer was used to measure blood lipid parameters,including triglyceride (TG),total cholesterol (TCh),high-density lipoprotein (HDL),low-density lipoprotein (LDL),small and low-density lipoprotein (sdLDL),lipoprotein (a),apolipoprotein A1 (ApoA1),and apolipoprotein B (ApoB). RT-qPCR was used to measure the mRNA expression of fatty acid synthase (FASN),acetyl-CoA carboxylase (ACACA),hydroxymethylglutarate mono-acyl CoA reductase (HMGR),ApoA1,ApoB,and low-density lipoprotein receptor (LDLR) in Huh7.5.1 cells with or without HCV infection. The t -test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results Compared with the control group,the experimental group had significantly lower serum levels of TCh (2.98±0.51 mmol/L vs 4.24±0.43 mmol/L,t=4.96,P <0.05),HDL (0.87±0.16 mmol/L vs 1.24±0.21 mmol/L,t=5.65,P <0.05),LDL (1.75±0.24 mmol/L vs 2.64±0.37 mmol/L,t=3.88,P <0.05),ApoA1 (0.94±0.18 mmol/L vs 1.47±0.26 mmol/L,t=3.71,P <0.05),and ApoB (0.67±0.31 mmol/L vs 0.98±0.14 mmol/L,t=4.41,P <0.05). Huh7.5.1 cells with HCV infection had significantly lower mRNA expression of ApoA1 than those without HCV infection ( t=-3.43,P <0.05),as well as significantly higher mRNA expression of FASN,ACACA,HMGR,ApoB,and LDLR ( t =5.40,4.93,3.34,6.88,and 3.84,all P <0.05). Conclusion HCV infection can upregulate the mRNA levels of enzymes involved in the synthesis of fatty acids and cholesterol and thus affect lipid metabolism in vivo and in vitro.