Résumé
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.
Résumé
<p><b>AIM</b>To explore the role of clonidine (Clo) on myocardial Gs alpha mRNA expression after scalds in rats.</p><p><b>METHODS</b>A 30% skin-full-thickness scald was produced by immersing rats in 95 degrees C water for 10 s. The myocardial Gs alpha mRNA expression level, cyclic AMP content and adenylyl cyclase (AC) activity were determined with dot blotting hybridization, in situ hybridization, radioimmunoassay and indirect method.</p><p><b>RESULTS</b>Three hours after scalds, the myocardial Gs alpha mRNA was significantly decreased to (61 +/- 20)% of the control group (P < 0.01). AC activity and cAMP content were also decreased. Clo (0.3, 1.0 and 3.0 mg.kg-1, i.p.) was shown to increase myocardial Gs alpha mRNA expression level (P < 0.01 or P < 0.05) after scalds to (131 +/- 28)%, (142 +/- 51)% and (139 +/- 48)% of the scald group, respectively, which were correlated with the Clo dose (gamma = 0.597, P < 0.05). Clo 1.0 mg.kg-1 and 3.0 mg.kg-1 (i.p.) promoted AC activity and increased cAMP content, but Clo 0.3 and 0.1 mg.kg-1 showed no significant effect (P > 0.05). Selective I1-imidazoline receptor antagonist efaroxan (Efa) (10, 5 mg.kg-1, i.p.) was found to partially reverse the effect of Clo, while Efa 2.5 mg.kg-1 showed no significantly influence. The reduced quantity of Gs alpha mRNA expression level correlated well with the Efa dose (gamma = 0.900, P < 0.05). The change of AC and cAMP was similar to Gs alpha mRNA.</p><p><b>CONCLUSION</b>Clo increased the myocardial Gs alpha mRNA expression, AC activity and cAMP content after scalds in rats.</p>