抗HMGB1抗体对小鼠肝纤维化的保护作用

Protection Effect of Anti-HMGB1 Antibody Against Mouse Liver Fibrosis

目的:探讨HMGB1在CCL4导致的肝纤维化发生发展中的作用及作用机制。方法:昆明种雄性小鼠30只,随机分为3组:正常组、CCL4肝纤维化组、抗HMGB1抗体组,建模8周后取肝组织及血清。用ELISA法检测血清中HA、Col-Ⅰ、PⅢP和IL-6、TNF-α的含量;用HE染色和天狼猩红染色观察肝组织病理改变和胶原纤维形成情况;用Real time RT-PCR法检测小鼠肝组织中TGF-β、α-SMA和MMP-9mRNA的表达。结果:CCL4肝纤维化组小鼠血清HA、Col-Ⅰ、PⅢP、IL-6、TNF-α含量和肝组织TGF-β、α-SMA和MMP-9mRNA表达均明显高于正常组小鼠(P<0.05);而且抗HMGB1抗体组小鼠血清HA、Col-Ⅰ、PⅢP、IL-6、TNF-α含量和肝组织TGF-β1、α-SMA和MMP-9mRNA表达均明显低于CCL4肝纤维化组小鼠(P<0.05)。结论:抗HMGB1抗体可减轻小鼠肝纤维化,减少小鼠炎症因子和纤维化因子的表达;HMGB1可能通过启动炎症反应而促进肝纤维化发生发展。

Objective：To investigate the role and mechanism of HMGB1 in mouse liver fibrosis induced by CCL4.Methods：Thirty Kunming mice were randomly divided into three groups：the normal group,the CCL4 liver fibrosis group,and Anti-HMGB1 group.Mice in each group were sacrificed after eight weeks.The parameters of plasma HA,Col-Ⅰ,PⅢP,IL-6,and TNF-αwere measured by ELISA.The morphological changes of the liver tissue were observed by HE staining and Sirius red staining.The levels of TGF-β,α-SMA and MMP-9mRNA were detected by Real time RT-PCR.Results：Compared with the normal group,the levels of plasma HA,Col-Ⅰ,PⅢP and IL-6,TNF-αand the liver mRNA expressions of TGF-β,α-SMA and MMP-9in CCL4 liver fibrosis group were significantly increased（P〈0.05）.Moreover,the levels of plasma HA,Col-Ⅰ,PⅢP and IL-6,TNF-αand the liver mRNA expressions of TGF-β,α-SMA and MMP-9in CCL4 liver fibrosis group were remarkably decreased compared with the CCL4 liver fibrosis group（P〈0.05）.Conclusion：HMGB1antibody can reduce mouse liver fibrosis,the expressions of inflammatory factors and fibrogenic cytokine levels in mouse with liver fibrosis.So HMGB1 may induce mouse liver fibrosis by its inflammatory response.