乙型肝炎病毒X抗原表达与肝细胞凋亡的相关性  

Correlation of hepatitis B virus X antigen expression with liver cell apoptosis

作　　者：李程[1] 王永康 王昌源[1] 杜磊[1] 张晓慧[1] 董格峰[1] 

机构地区：[1]山东大学医学院山东大学附属传染病医院7科,济南250021 [2]山东省省立医院病理科

出　　处：《中华肝脏病杂志》2013年第4期252-256,共5页Chinese Journal of Hepatology

基　　金：济南市科学技术局资助项目（200807033-1）

摘　　要：目的探讨乙型肝炎病毒x蛋白（HBxAg）在HBV感染相关洼肝病患者疴隋进展和癌变过程中的作用。方法用免疫组织化学方法检测38例HBV慢性感染者（HBV携带者14例及慢性乙型肝炎患者24例）、20例乙型肝炎肝硬化（LC）和20例HBV相关性肝细胞癌（HCC）患者肝组织中HBxAg、Fas及其配体（FasL）的表达，分析HBxAg与Fas、FasL表达的相关性及其与患者病毒学指标和肝脏病理学改变的关系。肝脏炎症分级及纤维化分期按照Knodell标准。计数资料用X2检验及Fisher精确概率法，多个样本间的两两比较用X2分割法，等级资料用秩和检验，相关性分析采用Spearman等级相关分析。结果HBV慢性感染者、LC及HCC患者肝组织中HBxAg阳性率分别为71．1％、60．0％、65．0％，差异无统计学意义（x2=0．754，P〉0．05）。肝细胞中Fas和FasL阳性率分别为28．9%、20．0%、5．0％和36.8％、50．0%、60．0%，各组间差异均无统计学意义（x2值分别为4．667和2．988，P值均〉0．05）。三组患者肝组织淋巴细胞Fas表达的阳性率分别为68．4%、60．0％和90．0％，其中，肝癌患者的表达强度显著高于HBV慢性感染者（Z=-4．360，P〈0．01）。在LC重症炎症区域及部分HCC患者中可见HBxAg与FasL在同一区域表达。相关性分析显示，HBV慢性感染和LC患者中，HBxAg与Fas、FasL表达强度均具有相关f生（，值分别为0．304和0．368，P值均〈0．05），Fas与FasL的表达也存在相关性（r=0．448，P〈0．01）。HBxAg阳性率在高、中病毒载量组（分别为88．9％和69．2％）均明显高于低病毒载量组（为26．7％，P〈0．05）。结论HBxAg在HBV感染各期均起重要作用，早期主要上调肝细胞Fas表达并诱导肝细胞凋亡，使肝脏炎症坏死加重；后期主要上调肝细胞FasL表达并诱导免疫逃避。HBxAg和高病毒载量在HBV慢性感染者病情发展和癌变中起重要作用。Objective To study the roles of hepatitis B virus （HBV） X antigen （HBxAg） in development of HBV-related liver diseases and carcinogenesis. Methods Liver tissues were collected from patients with HBV infection （HBV carriers, n = 14; chronic hepatitis B （CHB）, n = 24）, HBV-related liver cirrhosis （LC,n= 20）, or hepatocellular carcinoma （HCC, n = 20）. Immunohistochemistry was used to detect the expression of HBxAg and the host apoptosis-related genes Fas and Fas ligand （Fas-L）. The correlations of HBxAg with HBV DNA level in serum, inflammation grade, and fibrosis stage were statistically analyzed. Liver inflammation grade and fibrosis stage were in accordance with Knodell standard.X2 test and Fisher＇s exact test were adopted in count data, X2 split method was adopted in pariwise comparisons between multiple samples,Rank-sum test was adopted in ranked data, Spearman rank correlation analysis was adopted in correlation analysis. Results The rates of HBxAg-positivity were similar between the patients with HBV infection （71.1%）, LC （60.0%）, and HCC （65.0%） （n = 0.754, P = 0.686）. The rates of Fas- and Fas-L：positivity in liver cells were also similar between the three groups （Fas： 28.9% vs. 20.0% vs. 5.0%,x2 = 4.667, P = 0.101; Fas-L： 36.8% vs. 50.0% vs. 60.0%,x2 = 2.988, P = 0.225）. However, the positive rate of Fas in lymphocytes of liver tissue was significantly higher in the HCC patients than in the HBV-infected patients （90.0% vs. 68.4%, Z = -4.360, P = 0.00001）. The expressions of HBxAg and Fas-L corresponded to regions of severe inflammation in tissues from LC patients and some HCC patients. Furthermore, the expression of HBxAg was positively correlated with Fas （r = 0.304, P = 0.02） and Fas-L （1- = 0.368, P = 0.004） in the HBV-infected patients and LC patients, and the expression of Fas was positively correlated with that of Fas-L （r = 0.448, P = 0.0004）. Patients with high and medium loads of HBV DNA showed significantly higher rates of HB

关 键 词：肝炎 乙型 慢性 肝炎病毒 乙型 免疫组织化学 细胞凋亡 HBXAG FAS 

分 类 号：R512.62[医药卫生—内科学]