Expression and Significance of BMP-7/Smads Signaling Pathway in Hepatic Fibrosis Tissues induced by Common Bile Duct Ligation in Rats / 医学研究杂志

ABSTRACT

Objective To investigate the expression and significance of BMP7/Smads signaling pathway in hepatic fibrosis tissues induced by common bile duct ligation in rats.Methods Male Wistar rats were simple randomizationally divided into sham operation group,common bile duct ligation group for 7days group,14days group,28days group and 42days group.Common bile duct ligation meth-od was used to establish the cholestatic hepatic fibrosis animal model.hematoxylin-eosin staining and Masson staining were used to ob-serve the hepatic tissues morphology and collagen deposition of the rats in each group.Real-time quantitative polymerase chain reaction(RT-qPCR)technology was used to detect the mRNA expression of hepatic fibrosis indicators,such as α-smooth muscle actin(α-SMA)and fibronectin(FN)in each group.Immunohistochemistry was used to determine the deposition of collagen Ⅰ in the hepatic tis-sues,Western blot was used to detect the proteins expression of FN,collagen Ⅰ,collagen Ⅲ,α-SMA and tissue inhibitor of matrix metalloproteinase(TIMP1)in the hepatic tissues.The expression and localization of BMP-7 and p-Smad1/5/8 proteins in the hepatic tissues were detected by Western blot and Immunohistochemistry.Results Compared with the sham operation group,with the extension of common bile duct ligation time,the degree of hepatic fibrosis gradually increased,the intrahepatic collagen hyperplasia was obvious,and thick fibrous septum were obviously formed in the hepatic issues of BDL groups.The expression of FN,α-SMA,collagen Ⅰ,colla-gen Ⅲ and TIMP1 proteins in the BDL hepatic tissues were significantly increased,the difference were statistically significant(P<0.05).In the hepatic fibrosis tissue,the expression of BMP-7 and p-Smad1/5/8 proteins were significantly increased in the early stage of hepatic fibrosis,while which were decreased with the aggravation of hepatic fibrosis.Compare with the sham operation group,the difference was statistically significant(P<0.05).Conclusion The BMP-7/Smads signaling pathway is significantly activated in the early stage of hepatic fibrosis in rats,which exerted protective effect on bile duct ligation-induced hepatic fibrosis.However,the protec-tive effect of activation of BMP-7/Smads signaling pathway was inhibited with the progression of hepatic fibrotic severity.