乙型肝炎病毒对肝内TGF-β_1/Smads信号通路的作用  

Role of hepatitis B virus in intrahepatic TGF-β_1/Smads signaling pathway

作　　者：张香梅[1] 乐晓华[1] 陈培芬[1] 苟继周[1] 孙炎[1] 钟荀珍 周亚敏[2] 刘晓玲[2] 陈青山[2] 

机构地区：[1]深圳市第三人民医院病理科,广东深圳518112 [2]暨南大学医学院流行病学教研室,广东广州510632

出　　处：《中国病理生理杂志》2013年第12期2218-2222,共5页Chinese Journal of Pathophysiology

基　　金：深圳市科技计划(医疗卫生类)(No.20103133;No.201202060)

摘　　要：目的:探讨乙型肝炎病毒(HBV)对肝内TGF-β1蛋白表达及Smads信号通路的作用,为制定慢性乙肝肝纤维化临床治疗策略提供理论依据。方法:(1)运用免疫组化PV-6000法检测对照组和慢性乙肝组肝组织中TGF-β1、HBsAg和HBcAg的表达,并采用荧光定量PCR法测定慢性乙肝患者血清HBV DNA含量。(2)应用体外细胞培养技术培养HBV刺激的人肝星状细胞系LX-2细胞,Western blotting方法测定其细胞内TGF-β1、Smad3和Smad7的蛋白表达。结果:(1)慢性乙肝组肝组织内TGF-β1的表达高于对照组(P<0.01);肝内TGF-β1表达水平与血清HBV DNA含量呈正相关(P<0.01),且HBcAg阳性肝组织水平较高(P<0.01)。(2)体外细胞学实验中,HBV刺激组LX-2细胞内TGF-β1和Smad3蛋白含量高于对照组和HBV+抗-TGF-β1组(P<0.01);Smad7蛋白表达差异无统计学意义(P>0.05)。结论:(1)TGF-β1在慢性乙肝患者肝组织中的表达与血清HBV DNA含量及肝内HBcAg的表达有关。(2)在TGF-β1/Smads信号通路中,HBV致纤维化作用机制以Smad3的正性调控为主,Smad7的作用不明显。[ ABSTRACT ] AIM： To explore the effects of hepatitis B virus （HBV） on intrahepatic expression of transforming growth factor β1 （TGF-β1） and Smads. METHODS： The expression of intrahepatic TGF-β1 , HBsAg and HBcAg in con- trol group and chronic hepatitis B （CHB） group was detected by immunohistochemical method. The serum HBV DNA con- tent was determined by real-time PCR. The role of HBV in the expression of TGF-β1 , Smad3 and Smad7 in human hepatic stellate cell line LX-2 in vitro was observed by cell culture and Western blotting. RESULTS ： The average score of intrahe- patic TGF-β1 expression in CHB group was higher than that in control group. With the increase in serum HBV DNA con- tent, intrahepatic TGF-β1 expression was also enhanced. In the HBcAg positive hepatic tissue, there was higher TGF-β1 expression than that in the liver tissue of HBcAg negative. Compared with control group and HBV ＋ anti-TGF-β1 group, HBV caused increased expression of TGF-β1 and Smad3 in HBV group in vitro. No difference of Smad7 protein among con- trol group, HBV group and HBV ＋ anti-TGF-β1 group was observed. CONCLUSION： The expression of intrahepatic TGF- β1 is related to serum HBV DNA and hepatocellular HBcAg in the patients with CHB. HBV-induced liver fibrosis mainly relies on positive regulatory mechanisms of Smad3, and the negative regulation by Smad7 almost does not function.

关 键 词：乙型肝炎病毒 转化生长因子 β1 Smad蛋白类 肝纤维化 

分 类 号：R363.21[医药卫生—病理学]