胆管部分梗阻致肝纤维化大鼠模型的建立

Experimental Rat Model of Hepatic Fibrosis Induced by Partial Bile Duct Obstruction

目的建立胆管部分梗阻致淤胆型肝纤维化大鼠模型。方法将SD大鼠36只,随机分为正常对照组(Normal,N)、假手术组(Sham,S)、胆管部分梗阻组(Partial Bile Duct Obstruction,PBDO)。PBDO组再分为1,2,3,4周组。PBDO组大鼠将胆总管部分阻断致胆管部分梗阻、胆汁淤积形成肝纤维化。N组及S组于术后1周、PBDO组分别于术后1,2,3,4周处死,各组动物取下腔静脉血检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、总蛋白(TP)及透明质酸(HA)、层粘连蛋白(LN)、Ⅳ型胶原(CIV)、Ⅲ型前胶原蛋白(PⅢP)。肝组织切片经HE和Van Gieson染色,观察病理变化和纤维增生情况。结果胆总管部分阻断后胆总管近端扩张、胆汁淤积。术后1周肝细胞水肿,毛细胆管及胆管上皮增生。术后2周汇管区可见胶原纤维增生。随着观察时间延长,汇管区胶原纤维增生及肝细胞变性逐渐加重。结论采用胆总管部分阻断可建立稳定的淤胆型肝纤维化大鼠模型。

Objective To establish a new model of hepatic fibrosis by using choledoch partial obstruction in rats.Methods Thirty-six SD mice were randomly divided into 6 groups,normal control（N）,sham（S）,partial bile duct obstruction（PBDO） groups.The liver biopsies were performed at week 1,2,3,4 after surgery and the hepatic fibrosis was assessed by H ＆ E and Van Gieson staining.The serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,total bilirubin（TBIL）,total protein（TP）,the serum levels of hyaluronic acid（HA）,procollagen type Ⅲ（PⅢP）,laminin（LN）,and Ⅳ collagen（CⅣ） content were determined at week 1,2,3,4 after surgery.Results After choledoch part obstruction,the proximal choledoch extended with bile siltation.The liver cells were degenerated,and collagenous fibers were seen in the hepatic portal area.And the collagenous fiber aggravated associated with worsen liver cell degeneration following the time of surgery.Conclusion By using choledoch partial obstruction,the rat model of liver fibrosis induced by partial biliary obstruction were successfully established