熊去氧胆酸改善胆汁淤积症幼鼠肝功能和抗肝纤维化的作用

Effect of Ursodeoxycholic Acid on Improvement of the Liver Function and Anti Hepatic Fibrosis in Immature Rats with Cholestasis

本研究试图通过制造幼鼠胆汁淤积症模型进而探讨熊去氧胆酸(ursodeoxycholic acid,UDCA)对胆汁淤积症幼鼠肝功能及肝纤维化指标的作用及影响。我们采用α-萘异硫氰酸酯(α-naphthyl isothiocyanate,ANIT)灌胃诱发幼鼠胆汁淤积症模型,检测经UDCA治疗后对大鼠肝功能各项生化指标、血清肝纤四项、肝组织免疫组化影响。结果提示造模组(ANIT Model)除胆碱酯酶(cholinesterase,CHE)外,肝功能各项指标均明显高于空白对照组(blank control)(p<0.01),表明造模成功;试验显示:γ-谷酰转肽酶(γ-glutamyl transpep tidase,γ-GT)、胆汁酸(total bile acids,TBA)在熊去氧胆酸治疗组(UDCA Treatment)中数值,明显较ANIT Model组降低,有统计学差异(p<0.05),而丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、间接胆红素(indirect bilirubin,IBIL)数值,相比ANIT Model组,无统计学差异;UDCA Treatment组血清层粘连蛋白(laminin,LN)、Ⅳ型胶原(collagenⅣ,cⅣ)明显低于ANIT Model组(p<0.01),而透明质酸(hyaluronic acid,HA)、Ⅲ型前胶原(procollagenⅢ,PCⅢ)与ANIT Model组相比均无统计学差异;UDCA Treatment组肝组织LN、cⅣ均明显低于ANIT Model组(p<0.01),有统计学意义。因此,通过本研究证明了UDCA有可能通过降低血清γ-GT、TBA改善肝功能,通过降低血清及肝组织中LN、cⅣ而起到抗肝纤维化作用。

In this research,we tried to discuss the effects of Ursodeoxycholic acid（UDCA） on improving liver function and liver fibrosis indexes of neonatal cholestatic rats through constructing neonatal cholestasis rats model.We used the intragastric administration of α-Naphthyl isothiocyanate（ANIT） to induce the neonatal cholestatic rat model.After UDCA treatment,we detected the liver function,liver fibrosis four indexes in serum and conducted liver immunohistochemistry analysis.Results showed that indicators of liver function（Alanine aminotransferase（ALT）,Aspartate aminotransferase（AST）,Total bilirubin（TBIL）,Direct bilirubin（DBIL）,Indirect bilirubin（IBIL）,γ-Glutamyl trans peptidase（γ-GT） and Total bile acids（TBA）） in ANIT model group were significantly higher t han those in blank control group（p〈0.01）,except Cholinesterase（CHE）,indicating the model was successful.γ-GT and TBA in UDCA treatment group were lower than those in ANIT model group（p〈0.05）,while ALT,AST,TBIL,DBIL and IBIL had no significant differences between UDCA treatment group and ANIT model group.Laminin（LN） and Collagen Ⅳ（cⅣ） in UDCA treatment group were lower than those in ANIT model group obviously（p〈0.01）.Hyaluronic acid（HA） and Procollagen Ⅲ（PCⅢ） had no significant differences between UDCA treatment group and ANIT model group.In liver immunohistochemistry staining,the IOD of LN,c IV in UDCA group were lower than those in ANIT model group significantly（p〈0.01）.Therefore,this study provided evidence that UDCA would ameliorate liver function by decreasing γ-GT and TBA in serum and have anti-liver fibrosis effect by lowering LN and cⅣ both in serum and hepatic tissues.