湖南中医药大学学报2025，Vol.45Issue(5)：836-844,9.DOI:10.3969/j.issn.1674-070X.2025.05.008
姜黄素通过Akt/mTOR/HIF-1α通路调控氧糖剥夺PC12细胞自噬的机制研究
Mechanism of curcumin in regulating autophagy in oxygen-glucose deprived PC12 cells through the Akt/mTOR/HIF-1α pathway
摘要
Abstract
Objective To explore the protective effects of curcumin on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC 12 cells and its mechanism.Methods An in vitro OGD-induced autophagic injury model was established in PC 12 cells,and the PC 12 cells were divided into CON group,OGD group,dexmedetomidine(DEX)group,and low-,medium-,and high-dose curcumin groups.Except for the CON group,cells in all other groups were switched to glucose-free DMEM medium and subsequently subjected to OGD treatment by incubating them for six hours under conditions of 94％N2,5％CO2,and 1％O2.The low-,medium-,and high-dose curcumin groups,along with the DEX group,were respectively intervened with curcumin at concentrations of 1.25,5,and 20 μmol/L,as well as 0.5 μmol/L DEX for 12 hours.The viability of PC12 cells was measured using the MTT assay.Transmission electron microscope was used to observe autophagosomes and autolysosomes following curcumin treatment,and the MDC staining method was employed to observe the fluorescence intensity of autophagosomes.Western blot was conducted to determine the relative expression levels of autophagy-related proteins,including microtubule-associated protein light chain 3(LC3)-Ⅱ/LC3-Ⅰ,Beclin-1,sequestosome 1(p62),phosphorylated protein kinase B/protein kinase B(p-Akt/Akt),phosphorylated mammalian target of rapamycin/mammalian target of rapamycin(p-mTOR/mTOR),and hypoxia-inducible factor 1α(HIF-1α).Results Compared with the CON group,the OGD group exhibited a significantly reduced cell viability(P＜0.01)and a markedly enhanced fluorescent intensity of autophagosomes in PC 12 cells(P＜0.01).The protein expression levels of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,and HIF-1αwere significantly upregulated(P＜0.01),while those of p62,p-Akt/Akt,and p-mTOR/mTOR were significantly downregulated(P＜0.01).Compared with the OGD group,the low-,medium-,and high-dose curcumin groups and the DEX group exhibited increased cell viability(P＜0.05,P＜0.01)and reduced autophagic fluorescence intensity in PC12 cells(P＜0.05,P＜0.01).Compared with the OGD group,the low-and medium-dose curcumin groups and the DEX group demonstrated significantly decreased protein expressions of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,and HIF-1α(P＜0.01),along with significantly elevated protein expressions of p62,p-Akt/Akt,and p-mTOR/mTOR(P＜0.01).Conclusion The low-and medium-dose curcumin groups can exert protective effects against neuronal autophagic injury by activating the Akt/mTOR pathway,subsequently modulating HIF-1α protein expression and inhibiting OGD-induced autophagic injury in PC12 cells.关键词
姜黄素/氧糖剥夺/细胞自噬/右美托咪啶/Akt/mTOR/HIF-α通路/自噬损伤Key words
curcumin/oxygen-glucose deprivation/autophagy/dexmedetomidine/Akt/mTOR/HIF-α pathway/autophagic injury分类
医药卫生引用本文复制引用
李晓凤,田梦芝,陈笑一,彭南波,陈思远,杜可..姜黄素通过Akt/mTOR/HIF-1α通路调控氧糖剥夺PC12细胞自噬的机制研究[J].湖南中医药大学学报,2025,45(5):836-844,9.基金项目
湖南省自然科学基金项目(2025JJ80168) （2025JJ80168）
湖南省普通高等学校教学改革研究项目(HNJG-2022-0134) （HNJG-2022-0134）
湖南中医药大学学科建设"揭榜挂帅"项目(22JBZ020). （22JBZ020）
