The Novel Mechanism Of Rapamycin Inhibition Liver Fibrosis In The Rat

Aims:To study the effect of rapamycin on liver fibrosis and the potential mechanism.Methods:(1) Rapamycin was administerd in certain time of Estabalished models of rat liver fibrosis induced by carbon tetrachloride.HE and immunohistochemistry ofα-SMA was made to identify the effect of rapamyein on liver fibrosis comparing to normal and fibrotic rat liver.(2) Hepatocytes were isolated and purified from normal,Fibrotic and Raparnycin treated group's rat.The expression of E-cadeherin,connexin43, vimentin,α-SMA,p-smad2,p-smad3,smad2/3 and smad4 was compared between the different group using western blot.Results:(1) Rapamycin could inhibit the liver fibrosis in carbon tetrachloride induced rat's model.(2) The expression of vimentin andα-SMA which are verified as mesenchymal markers increased while E-cadeherin and connexin43 that are deemed as epithelial markers decreased with more collagenⅠsecreted in hepatocytes of fibrosis rat's liver compared with hepatocytes of normal rat's liver.These indicated hepatocytes in fibrotic liver may transit an Epithelial to Mesenchymal Transition.(3) Rapamycin could inhibit EMT of hepatocytes in fibrosising liver as hepatocytes in treated group displayed lower mesenchymal marker and higher epithelial marker than that in the fibrotic liver.(4) The expression of p-smad2,p-smad3,smad2/3 and smad4 was upregulated in hepatocyte of fibrotic rat's liver and rapamycin could downregulated these proteins.Conclusion:Our study reveal that rapamycin could inhibit carbon tetrachloride induced liver fibrosis through blocking epithelial to mesenchymal transition of hepatocytes by downregulation of p-smad2,p-smad3,smad2/3 and smad4.