白头翁皂苷B4通过调控AMPK/ACC/CPT1A信号通路改善非酒精性脂肪肝小鼠氧化应激水平的研究OA
Study of anemoside B4 improving oxidative stress levels in mice with non-alcoholic fatty liver disease by regulating the AMPK/ACC/CPT1A signaling pathway
目的:探究白头翁皂苷B4(anemoside B4,AB4)对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)小鼠的干预作用及可能的分子机制.方法:采用高脂饮食构建NAFLD小鼠模型并以AB4进行干预.实验过程中监测小鼠体质量、葡萄糖耐量及胰岛素耐量;8周后收集血清、肝脏等组织样本,检测总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)及高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C);采用H&E染色及油红O染色观察肝脏组织病理学改变和脂质沉积情况;采用免疫荧光方法评估AB4对肝脏代谢性炎症的影响;qRT-PCR及Western blot法检测肝脏组织中腺苷酸活化蛋白激酶(adenosine 5'-monophosphate-activated protein kinase,AMPK)、乙酰辅酶A羧化酶(acetyl CoA carboxylase,ACC)、肉碱棕榈酰转移酶(carnitine palmitoyltransferase 1A,CPT1A)mRNA 及蛋白表达水平的变化;分析超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的水平.结果:AB4可明显降低高脂喂养小鼠的体质量,改善小鼠糖耐量异常情况,缓解胰岛素抵抗情况.AB4可改善TC、TG、LDL-C及HDL-C的病理变化;各给药组肝脏病理切片显示损伤程度减轻,肝脏脂肪空泡数量减少;血清MDA水平降低,SOD、GSH-Px水平升高;肝脏炎症因子白细胞介素-6表达减少.此外,给药组肝脏中AMPK、ACC、CPT1A mRNA及蛋白表达升高.结论:AB4能够调节肝脏脂肪代谢与血糖水平、减轻氧化应激反应,且其治疗NAFLD的潜在的作用机制可能与调控AMPK/ACC/CPT1A信号通路有关.
Objective:To explore the intervention effect of anemoside B4(AB4)on mice with non-alcoholic fatty liver disease(NAFLD)and its possible molecular mechanism.Methods:The NAFLD mouse model was established by a high-fat diet and was treated with AB4.During the experiment,the body weight,glucose tolerance,and insulin tolerance of the mice were monitored.After 8 weeks,serum,liver and other tissue samples were collected to detect total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C);Histopathological changes and lipid deposits in the liver were assessed using H&E staining and oil red O staining.Immunofluorescence was used to evaluate the effects of AB4 on liver metabolic inflammation.The mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),acetyl CoA carboxylase(ACC),and carnitine palmitoyltransferase 1A(CPT1A)in liver were detected by qRT-PCR and Western blot.The levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)were analyzed.Results:AB4 could significantly reduce the body weight of high-fat fed mice,improve the abnormal glucose tolerance of mice,and relieve insulin resistance.AB4 could improve the pathological changes of TC,TG,LDL-C,and HDL-C.The liver pathological sections of each administration group showed that the degree of injury was reduced,the number of hepatic fat vacuoles was reduced,the serum MDA level was decreased,the SOD and GSH-Px levels were increased,and the expression of liver inflammatory factor interleukin-6 was decreased.In addition,after AB4 interven-tion,the mRNA and protein expressions of AMPK,ACC,and CPT1A in liver of drug administration groups were increased.Conclusion:AB4 can regulate liver fat metabolism and blood glucose level,reduce oxidative stress response,and its potential mechanism of action in the treatment of NAFLD may be related to the regulation of the AMPK/ACC/CPT1A signaling pathway.
蒋鸣;田冲冲
江苏医药职业学院药学院,江苏 盐城 224005江苏医药职业学院药学院,江苏 盐城 224005
医药卫生
白头翁皂苷B4非酒精性脂肪肝氧化应激AMPK/ACC/CPT1A信号通路
Anemoside B4Non-alcoholic fatty liver disease(NAFLD)Oxidative stress responseAMPK/ACC/CPT1A signaling pathway
《海南医科大学学报》 2026 (2)
128-136,9
This study was supported by the 2023 Key Project of Medical Research of Jangsu Yancheng Commission of Health(YK2023032) 江苏省盐城市卫生健康委员会2023年度医学科研立项项目(YK2023032)
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