当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Effect of sirolimus on liver cirrhosis and hepatic encephalopathy of common bile duct-ligated rats.

Effect of sirolimus on liver cirrhosis and hepatic encephalopathy of common bile duct-ligated rats.

Abstract：

:Cirrhosis is often associated with portal hypertension and portal-systemic collateral vessels formation attributed to angiogenesis, which leads to severe complications as hepatic encephalopathy. Sirolimus has anti-fibrosis and anti-angiogenesis effects, but whether it influences the severity of portal-systemic collaterals and hepatic encephalopathy is unknown. This study was thus designed to address this issue in rats with common bile duct ligation-induced liver cirrhosis. Sham-operated rats were surgical controls. Rats were intraperitoneally administered with 0.5 and 2 mg/kg/day sirolimus or vehicle for 2 weeks. Four weeks post operations, motor activities, body weight, biochemistry and hemodynamic data were measured. The liver was dissected for histopathology, immunohistochemical stains and protein analysis. On the parallel cirrhotic groups, the portal-systemic shunting was determined. The results showed that the body weight gain was significantly lower in sirolimus-treated rats. Sirolimus reduced portal pressure and plasma levels of alanine aminotransferase, aspartate aminotransferase and ammonia, and attenuated hepatic inflammation and fibrosis in cirrhotic rats. In addition, the hepatic phosphorylated mammalian target of rapamycin (mTOR) and P70S6K protein expressions were significantly downregulated and endothelial nitric oxide synthase (eNOS) expression upregulated by sirolimus. Sirolimus did not influence portal-systemic shunting and motor activities of cirrhotic rats. In conclusion, sirolimus significantly improved hepatic inflammation and fibrosis accompanied by portal pressure reduction in cirrhotic rats, in which down-regulated mTOR/P70S6K and up-regulated eNOS expressions might play a role. However, sirolimus did not significantly change the severity of portal-systemic collaterals and motor activities, suggesting that the multifactorial pathogenesis of hepatic encephalopathy could not be fully overcome by sirolimus.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Wu KC,Huang HC,Chang T,Lee WS,Chuang CL,Hsin IF,Hsu SJ,Lee FY,Chang CC,Lee SD

doi

10.1016/j.ejphar.2018.02.016

subject

Has Abstract

pub_date

2018-04-05 00:00:00

pages

133-139

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(18)30094-3

journal_volume

824

pub_type

杂志文章

在线工具

Effect of sirolimus on liver cirrhosis and hepatic encephalopathy of common bile duct-ligated rats.