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[目的]通过对猪血清致大鼠免疫性肝纤维化模型的动态观察,探讨免疫性肝纤维化的形成机制。[方法]采用腹腔注射猪血清0.5 ml,每周2次;大鼠按体重随机分为正常对照组和模型组,在1、2、4、8和12周分别处死大鼠并取材,观测肝组织病理学、肝功能、羟脯氨酸(Hyp)水平。[结果]苏木精-伊红染色,随着刺激因素持续时间的延长,汇管区炎性细胞浸润增多和肝细胞损伤,肝星状细胞(HSC)数量增多并部分活化;天狼猩红染色,4周模型组纤维间隔明显,假小叶初步形成,8和12周模型组胶原增生明显,肝小叶形成;血清总蛋白(TP)和球蛋白(Glb)水平,1、2、4、8和12周模型组均较正常组显著升高(P<0.01);血清清蛋白(Alb)水平,与正常组相比,1、2、4、8周无差异,12周模型组显著降低(P<0.01);血清丙氨酸氨基转移酶(ALT)活性,与正常组相比,2、4周模型组差异有统计学意义(P<0.05),1、8和12周模型组无差异;Hyp水平,与正常组相比,1、2周模型组差异无统计学意义,4、8和12周模型组均有显著升高(P<0.01)。[结论]①腹腔注射猪血清4周时,肝纤维化初步形成,8周模型复制已经成功;②猪血清作为异种抗原侵入,刺激机体产生免疫反应,免疫球蛋白增加,是主动性的肝纤维化;③免疫反应激活HSC的活化,分泌合成胶原增生明显,从而形成肝纤维化。
[Objective] To investigate the dynamic mechanism of immune-induced hepatic fibrosis induced by pig serum in rats. [Method] 0.5 ml of pig serum was injected intraperitoneally twice a week. The rats were randomly divided into normal control group and model group by body weight. Rats were sacrificed at 1, 2, 4, 8, and 12 weeks, Histopathology, liver function, hydroxyproline (Hyp) levels. [Results] Hematoxylin-eosin staining showed that with the prolongation of the duration of stimulation, inflammatory cell infiltration and hepatic injury were increased in portal area and the number of hepatic stellate cells (HSC) was increased and partially activated. Sirius red staining, At 4 weeks, the fibers in the model group were obviously separated and the pseudolobules were initially formed. At 8 and 12 weeks, collagen hyperplasia and hepatic lobule were found in the model group. The contents of TP and Glb, 1, 2, 4, 8 and 12 (P <0.01). The level of serum albumin (Alb) was not significantly different at 1, 2, 4 and 8 weeks in the model group compared with the normal group (P < 0.01). Serum alanine aminotransferase (ALT) activity was significantly lower in the 2,4-week model group than in the normal group (P <0.05), but no difference was found in the 1,8 and 12-week model group Compared with the normal group, there was no significant difference between the model group and the model group at 1, 2, and 4 weeks (P <0.01). [Conclusion] ①After 4 weeks of intraperitoneal injection of porcine serum, hepatic fibrosis initially formed and 8 weeks of model replication was successful; ② Porcine serum as a foreign antigen invaded and stimulated the body to produce an immune response and increased immunoglobulin. It was an active liver fibrosis ; ③ immune response activated HSC activation, secretion of collagen secretion significantly, resulting in the formation of liver fibrosis.