乙型肝炎病毒核苷(酸)类似物多重耐药宿主免疫因子水平的研究

摘要

目的 通过检测核苷(酸)类似物多重耐药慢乙肝患者宿主固有免疫因子IFN-α、IFN-γ、Mov10和TRIM22的mRNA表达水平,探讨核苷(酸)类似物多重耐药乙型肝炎病毒(hepatitis Boirus,HBV)感染状态下宿主的固有免疫状态,分析核苷(酸)类似物抗HBV多重耐药的宿主免疫分子机制.方法 收集就诊于黑龙江省医院感染内科门诊及病房确定核苷(酸)类似物耐药患者28例,其中多重耐药者18例,交叉耐药者10例,选择健康对照者20例,采集外周血.应用RT-RCR方法检测耐药患者及健康对照者外周血PBMC中固有免疫因子IFN-α、IFN-γ、Mov10和TRIM22的mRNA的表达水平,统计学分析这些固有免疫因子表达水平高低的意义.结果 耐药组外周血PBMC中固有免疫因子Mov10和TRIM22的mRNA表达均高于正常对照组,具有统计学意义(P<0.01);耐药组TRIM22 mRNA与其余三个因子IFN-α、IFN-γ、Mov10的mRNA表达均呈正相关;Mov10与TRIM22、IFN-α 的mRNA表达呈正相关;IFN-α 与IFN-γ、Mov10、TRIM22的mRNA表达呈正相关.多重耐药组与交叉耐药组固有免疫因子IFN-α、IFN-γ、Mov10和TRIM22的mRNA表达比较无显著性差异.结论 耐药组Mov10和TRIM22的mRNA表达高于正常对照组,HBV感染状态下,核苷(酸)类似物耐药中IFN-α、IFN-γ、Mov10、TRIM22等固有免疫因子间具有不同的相关性.%Objective In this study, the mRNA of interferon ( IFN)-α, IFN-γ, Mov10 and TRIM22, which are innate immune factors, was detected in chronic hepatitis B patients with nucleoside analogues multidrug resistance to investigate host innate immune status and explore the host immune molecular mechanism under the nucleos(t) ide analogues multiresistant HBV infection. Methods Twenty eight nucleos(t)ide analogue resistant patients and 20 healthy individuals in the control group were collected from infection medical clinic department of Heilongjiang provincial hospital. There were 18 cases of multiple drug resistance and 10 cases of cross resistance. Their peripheral blood specimens were collected. The mRNA of IFN-α, IFN-γ, Mov10 and TRIM22, that are the innate immunity factors in peripheral blood, were detected in 28 nucleos(t)ide analogue resistant patients and 20 healthy individuals using RT-PCR and the data were analyzed by statistical mthods. Results The mRNA levels of Mov10 and TRIM22 mRNA that are innate immune factors in peripheral blood mononuclear cells of multidrug resistant chronic hepatitis B patients were higher than those of control groups with statistically significant differences ( P < 0. 01). TRIM22 mRNA in chronic hepatitis B patients with multidrug resistance showed positive correlation with IFN-α, IFN-γ and Mov10 mRNA; Mov10 mRNA showed positive correlation with TRIM22 and IFN-αmRNA; IFN-α mRNA showed positive correlation with IFN-γ, Mov10 and TRIM22 mRNA. There were no statistically significant differences in the innate immunity factors IFN-α, IFN-γ, Mov10 and TRIM22 mRNA between multidrug resistant group and cross-resistant group. Conclusions The mRNA levels of Mov10 and TRIM22, that are innate immune factors, were higher in chronic hepatitis B patients with nucleos( t) ide analogues resistance than those of healthy control group. The correlation analysis of mRNA levels between IFN-α, IFN-γ, Mov10 and TRIM22 expression demonstrated that the correlations among them were different under the nucleoside analogues resistant HBV infection.