【摘要】 目的:研究人参皂苷Rg₁对PC-12细胞缺氧缺糖（oxygen-glucose deprivation,OGD）损伤的保护作用,并初步探讨与mTOR/Akt调控FoxO3核浆穿梭相关的可能的分子机制。方法:建立OGD损伤PC-12细胞模型,MTT法检测OGD对PC-12细胞存活率。人参皂苷Rg₁10,20,40μmol·L^-1预处理PC-12细胞24 h,加OGD损伤,MTT检测细胞存活率,比色法检测乳酸脱氢酶（LDH）释放、超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量。Western blot法检测mTOR,p-Akt^ser473,p-Akt^thr308,Akt,p-FoxO3,细胞核、细胞质FoxO3和总FoxO3蛋白表达。结果:OGD作用4²4 h显著抑制PC-12细胞增殖,呈时间依赖性。Rg₁(20,40μmol·L^-1)预处理24 h可显著增加细胞存活率,减少LDH释放,增加SOD活力和降低MDA含量。Rg₁可抑制由OGD引起的mTOR,p-Akt^ser473表达降低。OGD 6 h可减少FoxO3磷酸化,并促进细胞质FoxO3进入细胞核;预处理Rg₁增加FoxO3磷酸化,促进FoxO3进入细胞质。提示Rg₁可经由调控mTOR/Akt/FoxO3信号通路抑制PC-12细胞损伤。结论:人参皂苷Rg₁可抑制OGD引起PC-12细胞损伤,作用机制可能与激活mTOR/Akt信号通路调控FoxO3核质穿梭密切相关。更多还原

【Abstract】 Objective:To investigate the protective effect of ginsenoside Rg,on oxygen-glucose deprivation（OGD） in PC-12 cells,and preliminarily discuss the potential molecular mechanism of mT0R/Akt/FoxO3 signaling pathway.Method;The OGD PC-12 cell model was established.The cell viability was measured by MTT assay.After the pretreatment with Rg₁ with the concentration of 10,20,40 μmol·L^-1 for 24 h,the cell viability was observed.Lactate dehydrogenase（LDH） release,superoxide dismutase（SOD） activity and malondialdehyde（MDA） level were detected by colorimetry assay.mTOR,p-Akt^ser473,p-Akt^thr308,Akt,p-FoxO3,FoxO3 in cytoplasm and nucleus,and total FoxO3 protein expression were detected by Western blot assay.Result;OGD could significantly inhibit cell proliferation in 4-24 h in a time-dependent manner.After pretreatment for 24 h,Rg,（20,40 μmol·L ^） could notably elevate the cell viability and SOD viability and reduce the LDH release and MDA content.Besides,Rg,also inhibited OGD-induced mTOR and p-Akt^ser473 decreases.After treatment for 6 h,OGD could reduce FoxO3 phosphorylation and promote FoxO3 in cytoplasm.This data suggested that Rg,could protect PC-12 cell injury through mTOR/p-Akt/FoxO3 signaling pathway.Conclusion;Ginsenoside Rg,could attenuate OGD-induced PC-12 cell injury.Its action mechanism may be closely related to activation of mTOR/p-Akt/Fox03 signaling pathway.更多还原