中国药理学通报2023，Vol.39Issue(12)：2251-2257,7.DOI:10.12360/CPB202308063
卡维地洛调节ApoE-/-小鼠肝脏ACAD10、mTOR抗动脉粥样硬化
Carvedilol attenuates atherogenesis by regulating hepatic ACAD10 and mTOR in ApoE-/-mice
摘要
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 adminis-tered with vehicle or carvedilol 12.5 mg·kg-1 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 O staining,the level of blood glu-cose,blood lipids,aspartate aminotransferase(AST),alanine aminotransferase(ALT),and liver fatty acidβ-oxidase were determined,and glucose tolerance/in-sulin tolerance tests were performed as well.In addi-tion,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,glu-cose 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 ACAD 10 were significantly up-regulated,while mTOR was signifi-cantly down-regulated compared with that in the control group(P＜0.01).Conclusions Our results indicate that carvedilol regulates mTOR and ACAD 10 in liver,which may contribute to the alleviation of fatty liver,and even atherogenesis.关键词
卡维地洛/动脉粥样硬化/ACAD10/脂肪肝/mTOR/脂肪酸β氧化Key words
carvedilol/atherosclerosis/ACAD10/fat-ty liver/mTOR/oxidation of fatty acid beta分类
医药卫生引用本文复制引用
王鹏,袁瑶,张海港,刘雅..卡维地洛调节ApoE-/-小鼠肝脏ACAD10、mTOR抗动脉粥样硬化[J].中国药理学通报,2023,39(12):2251-2257,7.基金项目
重庆市自然科学基金资助项目(No cstc2019jcyj-msxmX0609) （No cstc2019jcyj-msxmX0609）
