肝组织TGF-β_1、TIMP-1及MMP-2表达与纤维化关系的实验研究

RELATIONSHIP BETWEEN LEVELS OF TGF-β_ 1 , TIMP-1 AND MMP-2 GENE EXPRESSIONS IN LIVER TISSUES AND FIBROSIS PATHOLOGY

目的 探讨免疫性肝纤维化肝组织TGF β1、TIMP 1及MMP 2表达与肝纤维化间的关系。方法 2 4只雄性Wistar大鼠尾静脉注射白蛋白建立实验性免疫性肝纤维化模型 ,检测血清HA、ALT、AST、ALB ,流式细胞仪定量分析肝组织TGF β1、TIMP 1、MMP 2和α SMA基因表达量 ,观察大鼠肝组织病理、肝组织Pollak三重染色和Gomori银染色、苦味酸 天狼红染色、Ⅳ型胶原免疫组化、α SMA免疫组化、肝匀浆Hyp测定。结果 随着肝纤维化程度的加重血清HA、ALT、AST、肝组织匀浆Hyp的浓度和TGF β1、TIMP 1及α SMA基因表达量均增加 ,MMP 2于肝纤维化早期明显升高 ,晚期明显降低。结论 实验性肝纤维化过程中TGF β1、TIMP 1促进肝纤维化的进展 ,MMP 2抑制其进展。

Objective To investigate the relationship between fibrosis pathology and the levels of TGF-β 1 , TIMP-1 and MMP-2 gene expressions in liver tissues. Method Dilution albumin was injected into the caudal vein of selected male Wistar rats to establish the model of experimental immuno-damaged hepatic fibrosis. The levelsof serum HA, AST, ALT and ALB, and liver homogenate hydroprolinewere examined, while the expressions ofα-SMA and collagen Ⅰ,Ⅲand Ⅳweredetermined by biochemical and immunohistochemical methods respectively. The TGF-β 1 , TIMP-1 and MMP-2 gene expressions in liver tissues were quantitatively analyzed by flow cytometry (FCM).Result With the increased degree of liver fibrosis, the levels of serum AST, ALT, HA, liver tissue homogenate HyP,as well as the levels ofTGF-β 1 , TIMP-1 and α-SMA gene expressions were increased. The level of MMP-2 gene expression was increased in the early and decreased in the late stage of fibrosis. Conclusion The study indicates that TGF-β 1 and TIMP-1 accelerate the development of experiment liver fibrosis, while MMP-2 suppresses the process.