WITHDRAWN: Effects of carvedilol on expression of TLR4 and its downstream signaling pathway in liver tissue of rats with cholestatic liver fibrosisjaundice.

Abstract

This study was designed to investigate the effects of carvedilol on the expression of TLR4 and its downstream signaling pathway in liver tissue of rats with cholestatic liver fibrosis, and provided experimental evidence for clinical treatment of liver fibrosis with carvedilol.? A total of fifty male Sprague Dawley rats were randomly divided into five groups (10 rats per group): sham surgery control group, bile duct ligation (BDL) model group, low-dose carvedilol treatment group (0.1mgkg-1d-1), medium-dose carvedilol treatment group (1mgkg-1d-1), high-dose carvedilol treatment group (10mgkg-1d-1). Rat hepatic fibrosis model was established by applying BDL. Forty-eight hours after the operation, carvedilol was administered twice a day. The blood and liver were simultaneously collected under the aseptic condition for further detection in two weeks after operation.? Compared with the sham group, the BDL group showed obvious liver injury, increased levels of inflammatory factors, and continued progression of liver fibrosis. Carvedilol could alleviate the above changes. The improvement effects were augmenting as dosages increasing. In addition, compared with the BDL group, carvedilol can reduce the expressions of TLR4, MyD88 and NF-?B p65 in liver tissue and increase the expression of ?-arrestin2, and the effect in the high dose group was more obvious. Carvedilol can reduce the release of inflammatory mediators by down-regulating TLR4 expression and inhibiting its downstream signaling pathway, thus playing a therapeutic role in cholestatic liver fibrosis.