乙型肝炎病毒相关性肾炎患者肾小管上皮细胞凋亡的病理学特点

Pathological study on renal tubular epithelial cell apoptosis in patients with hepatitis B virusassociated glomerulonephritis

目的探讨在乙型肝炎病毒(HBV)相关性肾炎(HBV-GN)中,HBV X(HBx)蛋白与肾小管上皮细胞凋亡之间的关系及其可能的信号机制。方法采用TUNEL法检测HBV-GN患者肾组织中细胞凋亡情况,并计算凋亡指数(AI)。采用免疫组织化学方法检测肾组织HBx蛋白、信号转导子和转录活化子3(STAT3)和磷酸化STAT3(p-STAT3)水平,并对肾组织HBx蛋白表达水平及其AI进行相关性分析。结果86%(19/22)的HBV-GN患者的肾小管上皮细胞内有HBx蛋白表达,而对照组无表达。HBV-GN组HBx蛋白、p-STAT3、STAT3、Bax的表达水平和AI均显著高于对照组(P值均<0.05),Bcl-2的表达水平和Bcl-2/Bax比值均显著低于对照组(P值均<0.05),且HBV-GN患者的AI与肾脏HBx蛋白表达(r=0.612,P=0.032)、24h尿蛋白定量(r=0.824,P=0.020)均呈正相关。结论肾小管上皮细胞凋亡是HBV-GN肾脏病理的重要病变之一。STAT3信号蛋白活化和Bcl-2/Bax比值降低可能参与其中。

Objective To investigate the correlation between hepatitis B virus（HBV）X protein（HBx）and renal tubular epithelial cell apoptosis in HBV-associated glomerulonephritis（HBV-GN）and the possible signaling mechanism.Methods Cell apoptosis in nephridial tissue of patients with HBV-GN was determined by terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling（TUNEL）method,then apoptosis index was calculated.HBx,phosphorylated signal transducers and activators of transcription 3（p-STAT3）and signal transducers and activators of transcription 3（STAT3）were determined by immunohistochemical assay.Correlation analysis was conducted between HBx expression in nephridial tissue and apoptosis index.Results There was no HBx expression in control group,whereas HBx was expressed in 86% HBV-GN patients（19/22）.The expressions of HBx,p-STAT3,STAT3 and Baxter（Bax）,and apoptosis index in HBV-GN group were significantly higher than those in control group（all P0.05）,while the expression of B-cell lymphoma-2（Bcl-2）and Bcl-2/Bax in HBVGN group were significantly lower than those in control group（both P 0.05）.Apoptosis index had linear correlation with HBx expression（r=0.612,P =0.032）and 24 hurine protein（r=0.824,P =0.020）.Conclusion Renal tubular epithelial cell apoptosis is one of the major pathological changes of HBV-GN.STAT3 signaling protein activation and decreased ratio of Bcl-2to Bax may be involved.（Shanghai Med J,2015,38：15-18）