二甲双胍改善高脂饮食诱导小鼠非酒精性脂肪肝的机制
Mechanism of Metformin improving non-alcoholic fatty liver in mice induced by high-fat diet
作者:
Author:
收稿日期: 年卷(期)页码:2020,35(04):-463-467
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:二甲双胍;中性粒细胞;非酒精性脂肪肝;CXCL14;CXCL16;高脂饮食;脂质代谢紊乱;动物模型
Key words:
基金项目:
中文摘要
目的研究二甲双胍改善肥胖诱导的非酒精性脂肪肝的作用机制。方法将21只C57BL/6J小鼠均分为对照组、高脂模型组、二甲双胍组。取肝脏称取重量,计算肝指数;用比色法测定血清中NEFA;用生化分析血清和肝脏组织中TG、ALT和AST的水平;用油红O染观察形态并观察病理变化;用WB检测SCD-1、FAS、SREBP-1、CPT-1和PACC蛋白的表达水平;用RT-PCR检测CXCL14、CXCL16的基因转录水平;免疫组织化学染色测定中性粒细胞(CD11b)的数量。结果二甲双胍抑制了高脂诱导的血清中NEFA的水平升高,减少了肝脏组织和血清中TG、AST和ALT的积累,改善了高脂诱导的小鼠病理状态,同时抑制SCD-1、FAS、SREBP-1蛋白水平和上调CPT-1、P-ACC蛋白水平;二甲双胍减少了高脂诱导的模型小鼠中性粒细胞CD11b的数量,同时抑制中性粒细胞趋化性蛋白CXCL14和CXCL16的基因转录水平。结论二甲双胍可能通过介导CXCL14和CXCL16的转录,抑制中性粒细胞对肝脏组织的浸润改善非酒精性脂肪肝。
参考文献
[1]刘玮亓,黄平.白藜芦醇对大鼠酒精性脂肪肝的保护作用[J].华西药学杂志,2017,32(3):264-266.
[2]Fan JG.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J].J Gastroenterol Hepatol,2013,28(Suppl1):11-17.
[3]Tailleux A,Wouters K,Staels B.Roles of PPARs in NAFLD:Potential therapeutic targets[J].Biochim Biophys Acta,2012,1821(5):809-818.
[4]Cusi K.Treatment of patients with type 2 diabetes and nonalcoholic fatty liver disease:Current approaches and future directions[J].Diabetologia,2016,59(6):1112-1120.
[5]Rouabhia S,Milic N,Abenavoli L.Metformin in the treatment of non-alcoholic fatty liver disease:safety,efficacy and mechanism[J].Expert Rev Gastroenterol Hepatol,2014,8(4):343-349.
[6]Xu H,Zhou Y,Liu Y,et al.Metformin improves hepatic IRS2/PI3K/Akt signaling in insulin-resistant rats of NASHand cirrhosis[J].J Endocrinol,2016,229(2):133-144.
[7]Kim E,Liu NC,Yu IC,et al.Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1gene expression with altered insulin sensitivity[J].Diabetes,2011,60(5):1493-1503.
[8]Li Y,Xu S,Mihaylova MM,et al.AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice[J].Cell Metab,2011,13(4):376-388.
[9]王昱.油橄榄叶提取物对非酒精性脂肪肝小鼠脂肪酸β氧化限速酶CPT-1表达的影响[J].西北民族大学学报:自然科学版,2018,109(1):15-19.
[10]Bijnen M,Josefs T,Cuijpers I,et al.Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice[J].Gut,2018,67(7):1317-1327.
[11]Alexander W,Christer B,Florian U,et al.Pharmacological inhibition of the chemokine CXCL16 diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury[J].Plo S One,2014,9(11):e112327.
上一条:阿片类药物相关性便秘的治疗药物研究进展
【关闭】