Role of sirolimus in fibrogenesis inhibition in secondary biliary cirrhosis. Experimental model in rat

Abstract

Background Chronic hepatopaties are characterized by progression to secondary fibrosis because of extracellular matrix protein deposit EMP EMP is produced by myofibroblasts cell type like stellate hepatic cell SHC mediated by mammalian target of rapamycin mTOR platelet derived growth factor PDGF transforming growth factor TGF beta Sirolimus is an immunosuppressant that inhibits mTOR and is believed to inhibit PDGF and TGF beta Methods Double blind randomized controlled assay control n and sirolimus n Bile duct ligation BDL was done to both groups biopsies were taken on th and th postoperative day and blood tests on the th day Sirolimus group was initiated at dose mg kg day Final biopsies were evaluated for proliferating bile ducts area as a pre fibrotic marker Results Bilirubin alanine aminotransferase ALT and aspartate aminotransferase AST were significant increased in Control Group Control group showed extensive cholangioles proliferation in Portal space with extension to hepatic lobule The proliferating ducts area in Portal space were micro m in Control Group and micro m in Sirolimus Group p lt Discussion and conclusion Anti proliferative effect of Sirolimus was demonstrated in the pre fibrotic phase in a secondary biliary cirrhosis model in rat The role of Sirolimus as antifibrogenic therapy in patients with biliary cirrhosis is not yet known