[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0.5ml,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 study the mechanism of immune liver fibrosis in rats induced by porcine serum with dynamic observation. [Methods] The rats were devided into normal group and model group randomly according to the weight. Liver fibrosis in rats was induced by intraperitoneal injection of porcine serum, twice per week. 5 rats( 2 in normal group and 3 in model group) were separately sacrificed for dynamic study after 1, 2, 4, 8 wk of modeling. The rest rats were sacrificed and sample was obtained for determination at the end of 12 wk. Pathological changes and collagen stain of the liver were observed under microscope. Liver function and hydroxyproline content in liver tissue were determined biochemically. [Results] With the prolonging of modeling, inflammatory cells infiltrating were seen by haematoxylin and eosin staining. Hepatocytes were swollen and hepatic stellate cells were activated and the numbers increased in the portal zones. Fibrous septa extending from portal area to liver lobule to form thin and complete fibrous septa were seen in liver tissue of rats with 4 weeks modeling by siriue staining. Similar changes were also seen in liver tissue of rats with 8 and 12wk modeling with obvious thickened fibrous septa. Compared with the normal group, TP and Glb content in rats of the 1, 2, 4, 8, 12wk modle group increased significantly(P〈0. 01); Alb content in the 12wk model group decreased markedly (P〈0. 01), there were no changes in the 1, 2, 4, 8wk modle group; Serum ALT activity in the 2wk group had obvious difference(P〈0. 05), and that in the 4wk had extreme difference(P〈0. 01), there were no differences in 1, 8, 12wk modle group; Hyp content in 4, 8, 12wk modle group increased significantly(P〈0. 01), there were no differences in 1, 2wk modle group. [Conclusion] Fibrosis in rats induced by continous injection of porcine serum is formed in the 4wk. Liver fibrosis in rats induced by porcine serum is initiative with globulin increasing. Immunoreaction stimulates hepatic stellate ce