基于MAVS介导信号通路的补肾方抗炎抗HBV作用及机制研究  

Anti-inflammation antiviral effects and mechanisms of Bushen recipe based on MAVS mediated signal pathway

作　　者：张景豪 郑超[1] 朱晓骏[1] 张鑫[1] 周振华[1] 李曼[1] 高月求[1] 孙学华[1] ZHANG Jing-hao;ZHENG Chao;ZHU Xiao-jun;SUN Xue-hua(Shuguang Hospital Affiliated to Shanghai University of Traditional Chi-nese Medicine,Shanghai Key laboratory of Traditional Chinese Medicine (Shanghai, 201203)China)

机构地区：[1]上海中医药大学附属曙光医院上海市中医临床重点实验室,上海201203

出　　处：《中西医结合肝病杂志》2019年第2期155-158,I0010,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家自然科学基金项目(No.81673935;81673938;81774256);上海市科委科技支撑项目(No.16401970600);上海申康市级医院新兴前沿技术联合攻关项目(No.SHDC12016121)

摘　　要：目的:观察补肾方对刀豆蛋白A(ConA)诱导HBV转基因小鼠肝损伤的抗炎及抗HBV作用机制。方法:24只HBV转基因小鼠随机分为3组,模型组及补肾方组小鼠按照体重予以3μg/g ConA尾静脉注射,正常组予以相应量生理盐水,每周1次,连续4周。造模后,补肾方组小鼠予以补肾方汤剂2.25g/kg体重灌胃,正常组及模型组小鼠予以等量生理盐水,每天1次,连续4周。观察各组小鼠处理前后血清丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)、乙型肝炎病毒表面抗原(HBsAg)、乙肝肝炎病毒脱氧核糖核酸(HBV DNA)水平及肝组织病理变化,观察各组小鼠处理前后肝组织HBcAg表达及肝组织线粒体抗病毒蛋白(MAVS)介导信号通路关键蛋白表达。结果:补肾方可显著降低ConA诱导HBV转基因小鼠血清ALT、AST水平(P<0.01),减轻肝组织内炎性细胞的浸润及肝细胞的变性坏死;可显著降低小鼠血清HBsAg水平(P<0.05),降低肝组织内HBcAg的表达(P<0.001);可显著提高小鼠血清IFN-β水平(P<0.01),上调TBK-1、STING、pTAK-1(t183)的表达,下调TRADD的表达(P<0.05)。结论:补肾方具有减轻肝组织炎症、抗HBV作用,其作用机制与MAVS介导的信号通路有关。Objective:To observe the anti-inflammation and antiviral effects of Bushen recipe,and explore its mechanisms based on MAVS mediated pathway. Methods:HBV transgenic mice were randomly divided into three groups. The model group and the Bushen recipe group were i. v. injected ConA at a dose of 3μg/g once a week for four weeks,and the normal group were with nomal saline. When molds were made, mice in treatment group were administered with Bushen recipe at a dose of 2. 25g/kg once daily;while mice in normal group and model group were administered with water. Four weeks later,mice were sacrificed and blood serum were collected and ALT,AST,HBsAg,HBV DNA and IFN-β were assayed. Histological changes and epression of HBcAg were observed by HE and IHC. The proteins expression of MAVS mediated pathway were detected by western blot. Results:Bushen recipe can significantly reduce the serum ALT and AST level induced by ConA in HBV transgenic mice(P < 0. 01),reduce the infiltration of inflammatory cells in liver tissues,and alleviated the necrosis of liver cells. It can significantly reduce the serum HBsAg level of mice and reduce the expression of HBcAg in liver tissues(P < 0. 05, P < 0. 001). The expres-sion of TBK-1,STING and pTAK-1 were up-regulated,and TRADD was down-regulated(P < 0. 05). Conclusion:these reveal Bushen recipe has anti-inflammation and anti-HBV effects,the mechanism is related to the MAVS mediated signaling pathway.

关 键 词：补肾方 慢性乙型肝炎 抗炎 抗病毒 信号通路 

分 类 号：R285.5[医药卫生—中药学]