陕西科技大学学报2024,Vol.42Issue(5):60-66,76,8.
葛根素通过AMPK/mTOR通路激活自噬治疗小鼠高脂血症
Puerarin activates autophagy through AMPK/mTOR pathway to treat hyperlipidemia in mice
摘要
Abstract
The aim of this study was to investigate the mechanism of therapeutic effect of pu-erarin on Hyperlipidemia(HLP)model mice.C57BL/6J mice were randomly divided into blank Control group(Control),disease Model group(Model)and puerarin low-dose,medi-um-dose and high-dose groups(PUE-L,PUE-M,PUE-H).After the successful construction of the hyperlipidemia model,the mice were treated with puerarin for 4 weeks,and the changes of the lipid profile of the mice were detected by the kit.In addition,pathological changes of mouse liver tissues were observed,and key proteins in liver tissues were detected by Western blot.They included the expression levels of adenylate activated protein kinase(AMPK)and rapamycin mammalian target protein(mTOR)signaling pathway,sterol regulatory element binding protein(SREBP),a key regulatory protein of lipid metabolism,and microtubule-as-sociated protein light chain 3(LC3)and autophagy substrate(P62)during autophagy.Fur-ther,we used quantitative polymerase chain reaction(q-PCR)to detect the mRNA expres-sion of acetyl-CoA carboxylase(ACC),fatty acid synthetase(FAS),sterol regulatory ele-ment-binding protein-1c(SREGBP-1C)in liver tissue.And the expression levels of mRNA and inflammatory factors related to AMPK/mTOR signaling pathway.Compared with the model group,the levels of total cholesterol(TC),triglyceride(TG)and low density lipopro-tein cholesterol(LDL-C)in the serum of puerarin treated group were significantly de-creased,while the levels of high density lipoprotein cholesterol(HDL-C)were significantly increased.In liver tissue,the vacuole-like changes and lipid droplet accumulation were signifi-cantly reduced after puerarin intervention.After administration,the relative expression levels of ACC,FAS and SREBP-1c mRNA in liver tissue decreased,the expression levels of LPS and pro-inflammatory factors TNF-α and IL-8 decreased,while the expression levels of anti-inflammatory factors IL-4 and IL-10 increased.In addition,the protein levels of mTOR,SREBP and P62 were decreased,while the expression levels of AMPK,p-AMPK and LC3 were increased.In summary,the experimental results show that puerarin can effectively im-prove the blood lipid profile of hyperlipidemia model mice and reduce the inflammatory re-sponse.The mechanism of action may be related to the regulation of AMPK/mTOR signaling pathway by puerarin,which promotes the activation of autophagy.These findings provide a new perspective on the treatment of hyperlipidemia,especially in the use of plant medicine.关键词
高脂血症/葛根素/腺苷酸活化蛋白激酶(AMPK)/雷帕霉素哺乳靶蛋白(mTOR)信号通路/自噬/炎症Key words
hyperlipidemia/puerarin/AMPK/mTOR signaling pathway/autophagy/inflam-mation分类
医药卫生引用本文复制引用
李蕾,金妍伶,吕碧君,王月,陆芝梅,袁迪芬,吴月滢,袁嘉丽..葛根素通过AMPK/mTOR通路激活自噬治疗小鼠高脂血症[J].陕西科技大学学报,2024,42(5):60-66,76,8.基金项目
云南省重大科技专项计划项目(202102AE090031) (202102AE090031)