糜酶对实验性大鼠肝纤维化的影响  

Role of chymase in the pathogenesis of experimental liver fibrosis in rats

作　　者：张立华[1] 王昌源[1] 杜磊[1] 谭炳芹[2] 

机构地区：[1]济南市传染病医院,山东省济南市250021 [2]潍坊市人民医院,山东省潍坊市261000

出　　处：《世界华人消化杂志》2011年第23期2432-2436,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨糜酶在肝纤维化形成中的作用,为研发新型抗纤维化药物奠定基础.方法:30只♂Wistar大鼠随机均分为3组.模型组以DMN制作肝纤维化模型;干预组除应用DMN外,同时给予糜酶抑制剂;正常组以生理盐水作对照.实验结束时进行组织学检查、电镜观察、血清肝纤维化指标、转化生长因子-β1(TGF-β1)和糜酶样活性检测.结果:与模型组相比干预组肝内纤维间隔纤细,无明显假小叶.电镜显示干预组肝细胞损伤明显减轻,肝窦内胶原纤维较少.干预组血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、TGF-β1和肝内糜酶样活性均明显低于模型组(均P<0.05).结论:糜酶通过直接或间接诱导TGF-β1的产生在肝纤维化形成中发挥重要作用,糜酶将成为未来新型抗肝纤维化药物的作用靶点.AIM： To investigate the role of chymase in the pathogenesis of dimethylnitrosamine （DMN）- induced liver fibrosis in rats.METHODS： Thirty male Wistar rats were randomly divided into three groups. The model group was administered with 10% DMN. The interventional group was given soybean trypsin inhibitor （SBTI） after induction of liver fibrosis with DMN. The normal group was given normal sodium. Liver histological and ultramicroscopic changes were observed, and serum indices for liver fibrosis, serum transforming growth factor β1 （TGF-β1） and hepatic chymase-like activity were measured at the end of the experiment. RESULTS： Compared to the model group, the interventional group had narrower fiber separation and showed no typical pseudo-lobule. Transmission electron microscopy demonstrated that hepatic cell damage in the interventional group was lessened significantly as compared to that in the model group, and only scattered collagen fiber was observed in the sinus hepaticus. Serum levels of HA, LN, PC Ⅲ, C Ⅳ, TGF-β1 and hepatic chymase-like activity in the interventional group were significantly lower than those in the model group （all P 〈 0.05）. CONCLUSION： Chymase participates in the development of liver fibrosis possibly by direct or indirect induction of TGF-β1 and may be a promising therapy target for hepatic fibrosis.

关 键 词：糜酶 糜酶抑制剂 肝纤维化 转化生长因子-Β1 WISTAR大鼠 

分 类 号：R575.2[医药卫生—消化系统]