Carvedilol attenuates atherogenesis by regulating hepatic ACAD10 and mTOR in ApoE" " mice / 中国药理学通报

ABSTRACT

Aim To explore the effects of carvedilol on atherogenesis in mice. Methods Eight-week-old ApoE mice were placed on an atherogenic chow and randomly divided into control and carvedilol group. The mice in both groups were intraperitoneally administered with vehicle or carvedilol 12. 5 mg • kg once daily, respectively. After 10 weeks, histopathological alterations of brachiocephalic trunk, liver, pancreas and adipose tissues were assessed by hematoxylin and eosin and oil red 0 staining, the level of blood glucose, blood lipids, aspartate aminotransferase (AST) , alanine aminotransferase ( ALT) , and liver fatty acid P-oxidase were determined, and glucose tolerance/insulin tolerance tests were performed as well. In addition , hepatic mRNA and protein expression of ACAD10 and mTOR were detected by real-time PCR and Western blot, respectively. Results Compared with the control group, the area of atherosclerotic plaque ( P < 0. 01 ) and intima-to-media ratio ( P < 0. 05) in the carvedilol group all significantly de- creased , aortic damages were obviously improved, glucose and insulin tolerance were remarkably enhanced; moreover, HDL-C concentration in serum increased (P <0. 05) . Notably, HE and oil red 0 staining revealed that carvedilol almost completely reversed hepatic steatosis, increased liver fatty acid beta oxidase levels (P < 0. 01 ) , along with the reduction in ALT (P < 0. 01 ) and AST (P <0. 01) levels, even improvement of pancreatic and adipose impairments in ApoE mice. In carvedilol group, the mRNA (P <0. 01) and protein expression levels (P <0. 05) of ACAD10 were significantly up-regulated, while mTOR was significantly down-regulated compared with that in the control group (P <0. 01). Conclusions Our results indicate that carvedilol regulates mTOR and ACAD10 in liver, which may contribute to the alleviation of fatty liver, and even atherogenesis.