抗肝纤冲剂抑制免疫型肝纤维化小鼠Ⅳ型胶原蛋白的表达

Anti-hepato-fibrosis granules suppresses the expression of collagen Ⅳ α2 in the hepatic fibrosis tissue in mice induced by pig serum~

目的：以猪血清所致的免疫损伤肝纤维化小鼠模型探讨抗肝纤冲剂对肝组织Ⅳ型胶原蛋白表达的影响及其对纤维化小鼠的治疗作用。方法：雌性Balb／c小鼠分为5组：正常对照组、肝纤维化模型组、秋水仙碱组、抗肝纤冲剂低剂量组、抗肝纤冲剂高剂量组。除正常组外，其余各组均采用腹腔注射猪血清的方法制备肝纤维化小鼠模型。造模的同时分别用药物对小鼠进行干预治疗7周。7周末处死小鼠，取肝组织，经固定、切片、Masson特殊胶原染色，光镜观察。其他肝组织用于实时荧光定量PCR检测。结果：胶原特殊染色显示，抗肝纤冲剂治疗组与模型组相比，胶原纤维增生程度减轻；实时荧光定量PCR检测显示，各实验组小鼠的肝组织中c014a2基因的表达量，模型组是正常对照组的9．44±2．81倍，抗纤冲剂低剂量组是正常对照组的2．04±0．27倍；模型组是抗纤冲剂低剂量组的4．63±0．45倍，抗肝纤冲剂低剂量组与肝纤维化模型组之间差异具有统计学意义，肝组织中的Ⅳa2型胶原蛋白在mRNA表达水平降低。结论：抗肝纤冲剂可以抑制免疫损伤肝纤维化小鼠肝组织的胶原蛋白增生，减少Ⅳ砭型胶原蛋白的表达，提示抗肝纤冲剂对肝纤维化小鼠具有较明显的治疗作用。

Objective： To explore the role of anti-hepato-fibrosis granules on expression change of collagen Iga2 in hepatic fibrotic tissue in mice induced by immune injury and validate the therapeutic effect. Methods： Female Balb/c mice were randomly divided into 5 groups： normal group, hepatic fibrosis model group, colchicine group, low dose anti-hepato-fibrosis granules group and high dose anti-hepto-fibrosis granules group. The hepatic fibrosis model was induced by intraperitoneal iniection of pig serum （0. 5 ml/once, once a week, total 7 weeks） except for the normal control group. When the model was duplicated, the later three groups were treated with colchicine, anti-hepato-fibrosis granules once a day for 7 weeks. At the end of experimental course, the morphological features were observed by means of Masson staining and expression of collagen Ⅳ2 was detected using real time PCR. Results ： Histopathological assessment showed that collgen was looser in the animals treated with anti-hepato-fihrosis granules. Compared to normal control, the mRNA expression of collagen Iva2 in model mice was increased by 9.44±2.81 times, and down to 2.04±0.27 times due to the administration of low dose anti-hepato-fibrosis granules. Singnificant difference was detected in expression of collagen Ⅳ α2 between the model animals and low dose anti-hepato-fibrosis group. Conclusion： Anti-hepato-fibrosis granules have therapeutic potential for terating hepatic fibrosis in mice induced by pig serum, through suppressing synthesis of collagen Ⅳ α2.