柚皮素通过抑制Sirt1/AMPKα信号通路减轻乙醇诱导的小鼠肝脏脂肪变性  

Naringenin reduces ethanol-induced liver steatosis in mice by inhibiting the Sirt1/AMPKα signaling pathway

作　　者：王玮 陈熙[1] 杨淑媚 罗丹[1] 段雪辉[1] 李启祥[1] WANG Wei;CHEN Xi;YANG Shu-mei;LI Qi-xiang(Department of Gastroenterology,Jiangmen Central Hospital,Jiangmen,Guangdong,529030,China)

机构地区：[1]江门市中心医院消化内科,广东江门529030

出　　处：《中西医结合肝病杂志》2023年第10期894-898,903,共6页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：吴阶平基金会临床科研专项资助基金(No.320.6750.2021-01-29)。

摘　　要：目的:观察柚皮素(NAR)对乙醇诱导的小鼠肝脏脂肪变性的影响并探讨机制。方法:50只雄性KM小鼠随机分为5组,包括Control组、乙醇诱导组(EtOH组)、NAR治疗组(EtOH+NAR组)、NAR溶剂组(EtOH+vehicle组)、NAR联合白藜芦醇(RES)治疗(EtOH+NAR+RES组),每组小鼠10只。苏木精伊红染色观察肝脏脂肪质沉积积累变化,Western Blot分析沉默信息调节因子1(Sirt1)/腺苷酸活化蛋白激酶α(AMPKα)信号通路蛋白表达。细胞实验中,HepG2细胞分为RES组、NAR联合RES组(NAR+RES组)和阴性对照组(NC组)。透射电子显微镜观察脂肪质沉积积累。qRT-PCR检测脂肪合成标志物SREBP1、FASN、ACC、SCD1和脂肪酸β氧化标志物PPARα、CPT1α、UCP2的mRNA表达水平。结果:动物实验中,与Control组比较,EtOH组小鼠的肝组织胎质量明显增加(P<0.05),Sirt1和p-AMPKα(Thr172)蛋白水平明显增高(P<0.05)。与EtOH+vehicle组比较,EtOH+NAR组小鼠的肝脏组织脂质沉积减少,Sirt1和p-AMPKα(Thr172)蛋白水平降低(P<0.05)。与EtOH+vehicle组比较,EtOH+NAR+RES组小鼠肝脏组织脂质沉积变化不明显,而与EtOH+NAR组比较,EtOH+NAR+RES组小鼠肝脏组织脂质沉积明显增加。细胞实验中,与NC组比较,RES组细胞的脂质积累显著增加(P<0.05),脂肪合成标志物SREBP1、FASN、ACC、SCD1的mRNA表达增高,脂肪酸β氧化标志物PPARα、CPT1α、UCP2的表达降低(P<0.05);与RES组比较,NAR+RES组细胞的脂质积累降低(P<0.05),而SREBP1、FASN、ACC、SCD1的表达减少,PPARα、CPT1α、UCP2的表达增加(P<0.05)。结论:NAR通过抑制Sirt1/AMPKα信号通路的激活从而减轻乙醇诱导的小鼠肝脏脂肪变性。Objective:To observe the effect of naringenin(NAR)on ethanol-induced liver steatosis in mice and explore the mechanism.Methods:Fifty male Kunming mice were randomly divided into 5 groups,including Control group,EtOH group,NAR treatment group(EtOH+NAR group),NAR solvent group(EtOH+Vehicle group),NAR combined with resveratrol(EtOH+NAR+RES group),each group consisted of 10 mice.The changes of liver fat accumulation were observed by hematoxylin-eosin staining,and the protein expression of silencing information regulator 1(Sirt1)/adenosine-activated protein kinaseα(AMPKα)signaling pathway was analyzed by Western blot.In the cell experiment,HepG2 cells were divided into RES group,NAR combined with RES treatment group(NAR+RES group)and negative control group(NC group).Transmission Electron Microscopy was used to observe fat accumulation.mRNA expression levels of fat synthesis markers SREBP1,FASN,ACC,SCD1 and fatty acidβoxidation markers PPARα,CPTαand UCP2 were detected by qRT-PCR.Results:In animal experiments,compared with the Control group,the lipid deposition of the EtOH group was significantly increased(P<0.05),and the protein levels of Sirt1 and p-AMPKα(Thr172)were significantly increased(P<0.05).Compared with the EtOH+vehicle group,the liver tissue lipid deposition in the EtOH+NAR group decreased,and the protein levels of Sirt1 and p-AMPKα(Thr172)decreased(P<0.05).Compared with the EtOH+vehicle group,the liver tissue lipid deposition in the EtOH+NAR+RES group did not change significantly,while compared with the EtOH+NAR group,the liver tissue lipid deposition in the EtOH+NAR+RES group was significantly increased.In the cell experiment,compared with the NC group,the lipid accumulation of the RES group was significantly increased(P<0.05),the mRNA expression of fat synthesis markers SREBP1,FASN,ACC,and SCD1 increased,and the fatty acidβoxidation markers PPARα,CPT1α,UCP2 increased The expression decreased(P<0.05);compared with the RES group,the lipid accumulation of the NAR+RES group decreased(P<0.05),while t

关 键 词：柚皮素 Sirt1/AMPKα信号通路 酒精性肝脏脂肪变性 

分 类 号：R575.5[医药卫生—消化系统]