巨噬细胞移动抑制因子在急性肝衰竭小鼠肝脏炎症中的作用研究

Effect of Macrophage Migration Inhibitory Factor on Liver Inflammation in Mice with Acute Liver Failure

目的探讨巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)在急性肝衰竭(acute liver failure,ALF)小鼠肝脏炎症中的作用。方法将18只雄性小鼠随机分为正常组、模型组、MIF拮抗剂ISO-1组。采用D-氨基半乳糖联合脂多糖诱导小鼠ALF模型,检测3组小鼠血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)和总胆红素(total bilirubin,TBIL)水平,HE染色观察肝脏病理形态学改变,Tunel染色观察肝细胞凋亡情况。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测小鼠肝脏组织中的MIF、CXC趋化因子受体2(CXC chemokine receptor 2,CXCR2)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平,免疫荧光观察MIF的表达。结果模型组小鼠较正常组小鼠肝组织结构破坏程度明显增加,肝细胞凋亡增多,肝功能受损;ISO-1能够减轻肝组织损害,减少肝细胞凋亡。模型组小鼠肝组织中MIF、CXCR2、TNF-α表达水平明显升高,而ISO-1能够显著降低MIF、CXCR2、TNF-α的表达水平,差异均有统计学意义(P<0.05)。结论MIF在ALF中的表达显著升高,抑制MIF可以改善肝组织损伤及炎性细胞因子表达,表明MIF在ALF中起重要作用。

Objective To investigate the role of macrophage migration inhibitory factor(MIF)on liver inflammation in mice with acute liver failure(ALF).Methods Eighteen male mice were randomly divided into normal group,model group and MIF antagonist ISO-1group.D-galactose combined with lipopolysaccharide were used to induce ALF model.The serum levels of alanine aminotransferase(ALT)、aspartate aminotransferase(AST)and total bilirubin(TBIL)were detected.The pathological changes of liver were observed by HE staining and the apoptosis of liver cells was observed by Tunel staining.The levels of MIF,CXC chemokine receptor 2(CXCR2)and tumor necrosis factor-α(TNF-α)in mouse liver tissues were detected by enzyme-linked immunosorbent assay(ELISA)and the expression of MIF was observed by immunofluorescence.Results Compared with the normal group,the model group showed serious liver tissue structure damage,increased hepatocyte apoptosis and decreased liver function.ISO-1 reduced liver tissue damage and hepatocyte apoptosis.The expression levels of MIF,CXCR2 and TNF-αin liver tissue of mice in model group was significantly increased,while ISO-1 could significantly reduce the expression levels of MIF,CXCR2 and TNF-α,with statistical significance(P<0.05).Conclusion The expression of MIF is significantly increased in ALF,and inhibition of MIF can improve liver tissue injury and the expression of inflammatory factors,indicating that MIF plays an important role in ALF.