针刺研究2026，Vol.51Issue(8)：955-967,13.DOI:10.13702/j.1000-0607.20250909
基于AMPK/mTOR/ULK1通路探讨电针对肥胖小鼠肝脏自噬的影响
Effect of electroacupuncture on hepatic autophagy in obese mice based on the AMPK/mTOR/ULK1 pathway
摘要
Abstract
Objective To investigate the effect of electroacupuncture(EA)on hepatic autophagy in obese mice by regulating the adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/unc-51 like autophagy activating kinase 1(ULK1)signaling pathway.Methods C57BL/6J mice were randomly divided into normal group,model group and EA group,with 8 mice in each group.The obese mice model was established by feeding high-fat diet.Mice in the EA group received EA at bilateral"Zusanli"(ST36)and"Tianshu"(ST25)for 30 min,5 times a week for 4 consecutive weeks.The Lee's index and body mass of mice in each group were observed before and after treatment;fasting serum glucose was measured;the insulin tolerance test(ITT)was performed,and the area under the curve(AUC)was calculated;the levels of fasting insulin,serum low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),total cholesterol(TC),and triacylglycerol(TG)were detected by ELISA,and the insulin resistance index was calculated;the mass of mesenteric white adipose tissue(mWAT)and liver tissue was weighed;the morphological changes of mWAT and liver tissue were observed by HE staining;the lipid deposition in the liver tissue was observed by Oil Red O staining;the ultrastructure of liver tissue was observed by transmission electron microscopy;the protein expressions of p-AMPK/AMPK,p-mTOR/m TOR,ULK1,microtubule-associated protein 1 light chain 3 type Ⅱ(LC3-Ⅱ),autophagy-related 5(Atg5),autophagy-related 7(Atg7),and sequestosome 1(SQSTM1/p62)in liver tissue were detected by Western blot;the mRNA expressions of AMPK,mTOR,ULK1,LC3-Ⅱ,Atg5,Atg7,and p62 in liver tissue were detected by quantitative real-time PCR.Results Compared with the normal group,the model group showed significant increases in Lee's index,body mass,fasting blood glucose,fasting insulin,insulin resistance index,and ITT-AUC(P<0.01);increased serum TG,TC,and LDL-C levels(P<0.01);decreased serum HDL-C level(P<0.01);increased mWAT and liver mass(P<0.01);enlarged adipocytes with reduced cell number per unit area in mWAT;swollen and disorganized hepatocytes with numerous lipid droplets and vacuoles;extensive orange-red lipid deposition;mitochondrial shrinkage and reduced autophagic vacuoles;decreased AMPK mRNA and p-AMPK/AMPK protein expression(P<0.01);increased mTOR mRNA and p-mTOR/mTOR protein expressions(P<0.01);decreased mRNA and protein expressions of ULK1,LC3-Ⅱ,Atg5,and Atg7(P<0.01);and increased mRNA and protein expression of p62(P<0.01).Compared with the model group,the EA group showed significant reductions in Lee's index,body mass,fasting blood glucose,fasting insulin,insulin resistance index,and ITT-AUC(P<0.01);decreased serum TG,TC,and LDL-C levels(P<0.01);increased serum HDL-C level(P<0.01);reduced mWAT and liver mass(P<0.01,P<0.05);decreased adipocyte diameter and increased cell number per unit area in mWAT;no obvious lipid droplets or vacuoles in hepatocytes;reduced orange-red lipid deposition;normal mitochondrial structure,increased autophagic vacuoles,and occasional autophagosomes and autolysosomes;increased AMPK mRNA and p-AMPK/AMPK protein expressions(P<0.01);decreased mTOR mRNA and p-mTOR/mTOR protein expressions(P<0.01);increased mRNA and protein expressions of ULK1,LC3-Ⅱ,Atg5,and Atg7(P<0.01);and decreased mRNA and protein expressions of p62(P<0.01).Conclusion EA at ST36 and ST25 can promote hepatic autophagy in obese mice,and its mechanism may be related to the regulation of the AMPK/mTOR/ULK1 signaling pathway.关键词
肥胖/电针/AMPK/mTOR/ULK1信号通路/自噬Key words
Obesity/Electroacupuncture/AMPK/mTOR/ULK1 signaling pathway/Autophagy引用本文复制引用
张英溶,周仲瑜,夏郡妮,王艺霏,张子怡,廖璐璐,王佳捷..基于AMPK/mTOR/ULK1通路探讨电针对肥胖小鼠肝脏自噬的影响[J].针刺研究,2026,51(8):955-967,13.基金项目
湖北省科技计划项目(No.2025BCB024) （No.2025BCB024）
武汉市科技局知识创新专项项目(No.2023020201010172) （No.2023020201010172）
湖北中医药大学"双一流"建设重点类专项科研项目(No.2023ZZXT005) （No.2023ZZXT005）
第七批全国老中医药专家学术经验继承项目(No.国中医药办人教函[2021]272号) （No.国中医药办人教函[2021]272号）
国家中医药管理局全国名老中医(王华教授)传承工作室项目(No.QZ202301) （王华教授）
湖北省科技厅国际科技合作项目(No.2022EHB054) （No.2022EHB054）
