激活素A中和抗体对小鼠肝组织细胞因子表达影响

The effect of activin A neutralizing antibody on the expression of eytokines in liver tissue of the mouse

目的应用四氯化碳(CCl4)制备小鼠肝纤维化模型,再给以激活素A(ACTA)中和抗体,观察ACTA中和抗体对小鼠肝纤维化的抑制作用及相关细胞因子表达的影响。方法将健康雄性昆明小白鼠随机分为五组正常对照组、橄榄油对照组、CCl4模型组、ACTA中和抗体组及对照抗体组。采用免疫组化法测定肝组织ACTA、转化生长因子 β1(TGF β1)、α平滑肌激动蛋白(αSMA)及增殖细胞核抗原(PCNA)的表达;采用图象分析系统评估肝组织纤维化程度。结果与CCl4模型组和对照抗体组相比,ACTA中和抗体组肝组织ACTA、TGF β1及αSMA的表达减少(P <0 .0 1) ;PCNA染色阳性的肝细胞数增多(P <0 .0 1)。结论ACTA中和抗体中和ACTA的作用,可能通过减轻对肝实质细胞的生长抑制和凋亡诱导而发挥抗肝纤维化的作用,从而使肝纤维化形成的关键细胞—肝星状细胞(HSC)的细胞外基质(ECM)成分表达减少,进而使与之有关的细胞因子网络系统发生改变,肝纤维化程度减轻。

Objective Activin A neutralizing antibody(AANA) was given to CCl_4-induced mouse hepatic fibrosis model so as to verify whether AANA can inhibit the process of hepatic fibrosis of the mouse,and to assess expression changes of various kinds of cytokines after the injection of AANA in the process of hepatic fibrosis.Methods Studies were conducted in male Kun Ming mice. The mice were divided into 5 groups randomly. They were normal control group,olive oil control group,CCl_4 model group,AANA group and control antibody group. The expression of activin A,TGF-β_1,α-SMA and PCNA in the liver tissue were detected by immunohistochemical techniques; the degree of hepatic fibrosis was determined by image analysis.Results In comparison with the mice of the CCL_4 model group and the control antibody group, the mice in the AANA group showed the following effects:there was obvious reduction in the expressions of activin A,TGF-β1 and α_~SMA in liver tissue(P<0.01); the number of PCNA-positive cells was increased(P<0.01).Conclusion The AANA possibly could relieve growth inhibition and apoptosis induction of hepatocytes,and thereby suppress hepatic fibrogenesis through neutralizing the action of activin A, and then decrease the production of extracellular matrix by hepatic stellate cells to relieve the degree of hepatic fibrosis.