基于AMPK/SREBP-1c及PPARα信号通路的玳玳果黄酮调控脂质代谢作用机制研究  

Studies on mechanism of lipid metabolism regulation of Citrus aurantium var.daidai flavonoids extract based on AMPK/SREBP-1 and PPARαpathway

作　　者：马国萍[1,2] 陈丹 陈红[2] 熊朝栋[1] 余文静 MA Guo-ping;CHEN Dan;CHEN Hong;XIONG Chao-dong;YU Wen-jing(Department of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Cadre Special Department,Fujian Provincial Hospital,Fuzhou 350001,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]福建省立医院干部特诊科,福建福州350001

出　　处：《中草药》2021年第21期6598-6608,共11页Chinese Traditional and Herbal Drugs

基　　金：福建省自然科学基金项目(2018J01253);福建省医学创新项目(2016-CX-45);福建省科技计划项目(2010Y2004)。

摘　　要：目的探究玳玳果黄酮调控脂质代谢作用及其分子机制。方法建立预防性高脂血症(hyperlipidemia)大鼠病理模型,以非诺贝特、辛伐他汀为阳性对照药,考察玳玳果黄酮调控脂质代谢的作用,光镜下观察肝脏组织形态学;采用实时荧光定量RT-PCR法、Western blotting法检测大鼠肝脏腺苷酸激活蛋白激酶(adenosine monophosphate activated protein kinase,AMPK)、固醇调节元件结合蛋白-1c(sterol regulatory element binding protein-1c,SREBP-1c)及过氧化物酶增殖物激活受体α(peroxidase proliferators activate receptorsα,PPARα)信号通路相关基因、蛋白的表达。结果预防性给药玳玳果黄酮后,与模型组相比,各剂量玳玳果黄酮对高脂血症大鼠血脂及肝脏脂肪变性均有明显的改善作用(P<0.05、0.01);可促AMPK磷酸化,使其mRNA及蛋白表达水平明显升高(P<0.05、0.01);显著抑制并明显下调SREBP-1c、脂肪酸合成酶(fatty acid synthase,FAS)、乙酰辅酶羧化酶(acetyl CoA carboxylase,ACC)蛋白和mRNA表达水平(P<0.05、0.01);可促进PPARα、肉毒碱棕榈酰基转移酶-1(carnitine palmityl transferase-1,CPT-l)蛋白及mRNA表达水平升高(P<0.05、0.01)。结论玳玳果黄酮可有效改善脂质代谢紊乱,防治高脂血症。其作用机制是通过激活AMPK促其磷酸化,从而抑制脂质合成,促进脂肪酸氧化分解,由此减少脂肪沉积,发挥调控脂质代谢的作用。Objective To explore the lipid metabolism regulation effect and molecular mechanism of flavonoids from Daidai(Citrus aurantium L.var.daidai Tanaka)fruit.Methods The hyperlipidemia(HLP)rat pathological model was established,and Fenofibrate and Simvastatin were used as positive control drugs to explore the effect of different doses of flavonoids from Daidai fruit on the regulation of lipid metabolic mechanism.The morphology of liver tissues was observed by light microscope.Real-time quantitative PCR(qRT-PCT)and Western blotting were used to measure the mRNA and the protein levels that are related to adenosine monophosphate activated protein kinase(AMPK),sterol regulatory element binding protein-1c(SREBP-1c),and peroxidase proliferators activate receptorsα(PPARα)signal pathway of rat liver tissues respectively.Results As compared to the model group,the result showed dose dependency after preventive administration of flavonoids from Daidai fruit,each dose of flavonoids from Daidai fruit were significantly able to improve blood lipid and liver steatosis in the hyperlipidemia rats(P<0.05,0.01);promote the phosphorylation of AMPK,and increase the levels of mRNA and protein expression for AMPK significantly(P<0.05,0.01);significantly inhibit and down-regulate the levels of mRNA and protein expression for SREBP-1c,fatty acid synthase(FAS),and acetyl CoA carboxylase(ACC)(P<0.05,0.01);increase the levels of mRNA and protein expression for PPARαand carnitine palmityl transferase-1(CPT-1)(P<0.05,0.01).Conclusion The flavonoids from Daidai fruit can effectively improve lipid metabolism disorder and prevent hyperlipidemia.Its mechanism of action is to activate AMPK to promote its phosphorylation,which inhibits lipid synthesis and promotes the oxidative decomposition of fatty acids,thereby reducing fat deposition and regulating lipid metabolism.

关 键 词：玳玳果黄酮 脂质代谢 腺苷酸激活蛋白激酶 固醇调节元件结合蛋白 过氧化物酶增殖物激活受体 

分 类 号：R285[医药卫生—中药学]