摘要
目的探究大黄素甲醚(physcion,PHY)对酒精性肝损伤中SIRT1-AMPK通路的作用机制。方法采用Lieber-DeCarli酒精液体饲料慢性喂养10 d,加1次酒精灌胃建立酒精性肝损伤模型,观察肝脏形态及病理学变化,测量肝指数及小鼠血清中ALT、AST、TG水平,ELISA法检测IL-1β表达情况,Western blot法检测小鼠肝组织SIRT1、AMPKα、p-AMPKα、SREBP1c蛋白水平。结果与正常对照组相比,大黄素甲醚组、SRT1720组及AICAR组明显地抑制了酒精引起的ALT、AST、TG的增高,各给药处理组肝形态、脂肪蓄积、炎症细胞浸润也呈剂量依赖性优于酒精模型组。同时,各给药处理组抑制了IL-1β的水平。与酒精模型组相比,大黄素甲醚及SRT1720、AICAR均提高了SIRT1表达及AMPKα的磷酸化水平。此外,大黄素甲醚及SRT1720、AICAR降低了SREBP1c的表达。结论从SIRT1-AMPK表达水平的变化验证了大黄素甲醚可通过此信号通路来减轻酒精性肝损伤的脂肪变性损伤和炎症水平,从而缓解酒精性肝损伤进程。
Aim To investigate the effect of physcion on SIRT1-AMPK pathway in alcoholic liver injury in mice.Methods The alcoholic liver injury model was established by placing the mice on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol via gavage.All mice were sacrificed for the observation of morphological and pathological changes.Liver index were measured and the levels of serum ALT,AST and TG were assessed by the kits,and the changes of IL-1β were assessed by ELISA.The expressions of SIRT1,AMPKα,p-AMPKαand SREBP1c were detected by Western blot.Results Compared with control group,different doses of physcion and SRT1720(SIRT1 agonist)AICAR(AMPK agonist)markedly inhibited the increase of ALT,AST and TG.Liver morphology,fat accumulation,inflammatory cell infiltration in treatment groups were better than those in EtOH group.Meanwhile,the treatment groups inhibited the levels of IL-1β.Compared with EtOH group,the expressions of SIRT1,AMPKαphosphorylation in physcion,SRT1720 and AICAR groups all increased.Additionally,the expressions of SREBP1c in physcion,SRT1720 and AICAR groups decreased.Conclusion Physcion alleviates fat accumulation and inflammatory of alcoholic liver injury possibly through activating SIRT1-AMPK signaling pathway.
作者
王瑞婕
杨勇
白婷
WANG Rui-jie;YANG Yong;BAI Ting(Medical College of Dalian University,Dalian,Liaoning 116622,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第11期1557-1562,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81700523,81900532)
辽宁省自然科学基金指导计划项目(No 2019-ZD-0570)
大连市科技创新基金项目(No 2019J13SN114)。
