Increased serum urotensin Ⅱ(UⅡ) levels in human cirrhotic populations have been recently shown,but the long-term effects of UⅡ receptor antagonist on the cirrhosis have not been investigated.To investigate the ther...Increased serum urotensin Ⅱ(UⅡ) levels in human cirrhotic populations have been recently shown,but the long-term effects of UⅡ receptor antagonist on the cirrhosis have not been investigated.To investigate the therapeutic effects of urotensin Ⅱ receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCI4)- induced cirrhosis,the hepatic and systemic hemodynamics,liver fibrosis,the metalloproteinase-13 (MMP-13)/ tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio,hepatic Rho-kinase activity,and the endothelial nitric oxide synthase (eNOS) activity are measured in CCI4-cirrhotic rats treated with palosuran or vehicle for 4 weeks.Primary hepatic stellate cells (HSCs) are used to investigate the changes in UⅡ/UT expression and the in vitro effect of palosuran.Compared with the vehicle-treated cirrhotic rats,treatment with palosuran can reduce the portal pressure (PP),decrease the risk of liver fibrosis and the level of a smooth muscle actin,collagen-l (COL-I),and transforming growth factor β expression.However,treatment with palosuran can increase MMP-13/TIMP-1,pvasodilator- stimulated phosphoprotein (p-VASP),and p-eNOS expression.Moreover,in vitro UⅡ/UT mRNA expression increases during HSC activation.MMP-13/TIMP-1,COL-I,and p-VASP are inhibited after palosuran treatment Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis,which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.展开更多
基金the National Natural Science Foundation of China (No.81170408 to Diangang Liu)the Wang Baoen Liver Fibrosis Research Foundation of the China Hepatitis Prevention Foundation (No.20120124 to Diangang Liu)the China Postdoctoral Science Foundation (No.2012M510094 to Diangang Liu).
文摘Increased serum urotensin Ⅱ(UⅡ) levels in human cirrhotic populations have been recently shown,but the long-term effects of UⅡ receptor antagonist on the cirrhosis have not been investigated.To investigate the therapeutic effects of urotensin Ⅱ receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCI4)- induced cirrhosis,the hepatic and systemic hemodynamics,liver fibrosis,the metalloproteinase-13 (MMP-13)/ tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio,hepatic Rho-kinase activity,and the endothelial nitric oxide synthase (eNOS) activity are measured in CCI4-cirrhotic rats treated with palosuran or vehicle for 4 weeks.Primary hepatic stellate cells (HSCs) are used to investigate the changes in UⅡ/UT expression and the in vitro effect of palosuran.Compared with the vehicle-treated cirrhotic rats,treatment with palosuran can reduce the portal pressure (PP),decrease the risk of liver fibrosis and the level of a smooth muscle actin,collagen-l (COL-I),and transforming growth factor β expression.However,treatment with palosuran can increase MMP-13/TIMP-1,pvasodilator- stimulated phosphoprotein (p-VASP),and p-eNOS expression.Moreover,in vitro UⅡ/UT mRNA expression increases during HSC activation.MMP-13/TIMP-1,COL-I,and p-VASP are inhibited after palosuran treatment Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis,which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.
