TNFSF14及其受体LTβR和HVEM在病毒肝炎中的作用  

Role of TNFSF14 and its receptors LTβR and HVEM in pathogenesis of virus hepatitis

作　　者：李桂清[1] 尚宇航[1] 曹朝晖[1] 杨菲[1] 郑权友 王庆红[3] 许桂莲[1] 

机构地区：[1]第三军医大学基础部免疫学教研室,重庆400038 [2]第三军医大学附属大坪医院泌尿外科,重庆400042 [3]重庆医科大学附属儿童医院儿科研究所流式细胞室,重庆400014

出　　处：《中国免疫学杂志》2015年第12期1591-1594,共4页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(31270929);重庆市自然科学基金面上项目(cstc2013jcyj A10129)资助

摘　　要：目的:探讨TNFSF14(即LIGHT)及其受体LTβR和HVEM在暴发性病毒肝炎中的作用。方法:MHV-3感染易感小鼠建立暴发性病毒肝炎模型,通过HE染色和血清ALT水平的测定比较了LIGHT KO和WT两组小鼠的肝损情况;定量PCR技术检测了MHV-3感染C57BL/6小鼠后各时相点(0 h、12 h、24 h、48 h、72 h)肝脏和脾脏组织HVEM和LTβR的mRNA水平。流式细胞术检测了临床病毒性重症肝炎病人PBMC中HVEM和LTβR的表达情况。结果:MHV-3感染72 h后,WT小鼠的肝脏出现明显坏死灶,而LIGHT KO小鼠的肝脏则未见异常;LIGHT KO小鼠血清中的ALT浓度也显著低于WT组(P<0.01)。MHV-3感染48 h后,C57BL/6小鼠脾脏中HVEM及LTβR的mRNA水平均有显著升高(P<0.05);肝脏中LTβR表达在12 h时就有显著上调(P<0.01)。与之一致的是,临床重症肝炎病人PBMC中HVEM和LTβR的表达较正常人均有明显升高。结论:TNFSF14可能通过与其受体LTβR和HVEM的相互作用在病毒诱发的暴发性肝炎中扮演重要角色。Objective： To explore the role of TNFSF14 and its receptors LTβR and HVEM in the pathogenesis of virus hepatitis. Methods： Marine fulminant viral hepatitis model was established by infecting mice with MHV-3. Liver tissue destruction in LIGHT KO and WT mice were analyzed by HE staining and ALT levels in serum by automatic biochemical analyzer. The mRNA levels of HVEM and LTβR in the liver and spleen tissues in the indicated time points（ 0 h,12 h,24 h,48 h,72 h） were detected by quantitative-PCR. The expression of HVEM and LTβR on PBMC in patients with severe hepatitis were measured by flow cytometry. Results： In the MHV-3-induced murine fulminant hepatitis model,liver injury in LIGHT KO mice was obviously decreased than that of WT mice,and ALT levels was also significantly lower than that of WT mice（ P〈 0. 01）. The mRNA of HVEM and LTβR in the spleen were increased significantly after 48 h postinfection with MHV-3（ P〈 0. 05）; The level of LTβR mRNA in liver was significantly up-regulated in 12 h postinfection with MHV-3（ P〈 0. 01）. Compared to healthy volunteers,the expression of both HVEM and LTβR on PBMC in patients with severe hepatitis was remarkably enhanced. Conclusion： TNFSF14 and its receptors LTβR and HVEM play a critical role in the pathogenesis of viral fulminant hepatitis.

关 键 词：TNFSF14 LTβR HVEM 病毒性肝炎 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]