【摘要】 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。更多还原

【Abstract】 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.更多还原