钙调磷酸酶/转录因子EB抑制神经元凋亡对帕金森病的机制研究OACHSSCD
Mechanisms of Inhibition of Neuronal Apoptosis via the Calcineurin/Transcription Factor EB Pathway in Parkinson's Disease
目的:探究钙调磷酸酶/转录因子EB(Calcineurin/TFEB)通路经微小核糖核酸-325-3p(microRNA-325-3p)抑制神经元凋亡对帕金森病细胞模型损伤的机制研究.方法:利用100 μmol/L1-甲基-4-苯基吡啶阳离子(MPP+)诱导的人神经母细胞瘤(SK-N-SH)细胞建立细胞模型,对比各组TFEB、microRNA-325-3p、Calcineurin、凋亡率、谷胱甘肽(GSH)、丙二醛(MDA)、环磷酰胺(CYC)、动力蛋白激活蛋白4(P62)、葡萄糖调节蛋白78(GRP78)、轻链3-Ⅱ/轻链3-Ⅰ(LC3Ⅱ/LC3 Ⅰ)水平含量.结果:较对照组,MPP+组 Calcineurin、凋亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 高,TFEB、microRNA-325-3p、GSH 低;MPP++NC 组凋亡率、MDA、CYC、P62、GRP78、LC3Ⅱ/LC3 Ⅰ 高,microRNA-325-3p、GSH 低;MPP++microRNA-325-3p 组 Calcineurin、凋亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 高,microRNA-325-3p、GSH 低;MPP++si-NC 组凋亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 高,TFEB、GSH 低;MP6P++si-Calcineurin/TFEB 组 Calcineurin、凋亡率、MDA、CYC、P62、GRP78、LC3Ⅱ/LC3 Ⅰ 高,TFEB、GSH 低.较 MPP+组,MPP++microRNA-325-3p 组 microRNA-325-3p、GSH 高,凋亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 低;MPP++si-Calcineurin/TFEB 组 TFEB、GSH 高,Calcineurin、凋亡率、MDA、CYC、P62、GRP78、LC3Ⅱ/LC3 Ⅰ 低.较 MPP++anti-NC 组,MPP++microRNA-325-3p+pcDNA 组、MPP++anti-microRNA-325-3p 组、MPP++microRNA-325-3p+pcDNA-Calcineurin/TFEB 组 TFEB、microRNA-325-3p、GSH 高,Calcineurin、凋亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 低;较 MPP++anti-microRNA-325-3p 组,MPP++microRNA-325-3p+pcDNA-Calci-neurin/TFEB 组 Calcineurin、调亡率、MDA、CYC、P62、GRP78、LC3 Ⅱ/LC3 Ⅰ 高,TFEB、microRNA-325-3p、GSH 低(P＜0.05).结论:microRNA-325-3p干扰Calcineurin/TFEB通路减轻细胞氧化应激,抑制神经元凋亡,增强细胞自噬,改善内质网应激及帕金森病细胞模型损伤,这可能成为治疗帕金森病的潜在分子靶点,为诊断及治疗帕金森病提供相关理论依据.
Objective:To investigate the mechanisms by which the calcineurin/transcription factor EB(calcineurin/TFEB)path-way inhibits neuronal apoptosis through microRNA-325-3p to alleviate damage in a cell model of Parkinson's disease.Methods:A cell model was established using human neuroblastoma(SK-N-SH)cells induced with 100 μmol/L 1-methyl-4-phenylpyridinium ion(MPP+).The levels of TFEB,microRNA-325-3p,calcineurin,apoptosis rate,glutathione(GSH),malondialdehyde(MDA),cy-clophosphamide(CYC),dynactin 4(P62),glucose-regulated protein 78(GRP78),and light chain 3-Ⅱ/light chain 3-Ⅰ(LC3-Ⅱ/LC3-Ⅰ)were compared among the different groups.Results:Compared with the control group,the MPP+group showed higher lev-els of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ,and lower levels of TFEB,microRNA-325-3p,and GSH;the MPP++NC group showed higher apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ levels,and lower mi-croRNA-325-3p and GSH levels;the MPP++microRNA-325-3p group showed higher levels of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ,and lower levels of microRNA-325-3p and GSH;the MPP++si-NC group showed higher apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ levels,and lower TFEB and GSH levels;and the MPP++si-calci-neurin/TFEB group showed higher levels of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ,and lower levels of TFEB and GSH.Compared with the MPP+group,the MPP++microRNA-325-3p group showed higher levels of microR-NA-325-3p and GSH,and lower apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ levels;the MPP++si-calcineurin/TFEB group showed higher levels of TFEB and GSH,and lower levels of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ.Compared with the MPP++anti-NC group,the MPP++microRNA-325-3p+pcDNA group,MPP++anti-mi-croRNA-325-3p group,and MPP++microRNA-325-3p+pcDNA-calcineurin/TFEB group showed higher levels of TFEB,microR-NA-325-3p,and GSH,and lower levels of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ;compared with the MPP++anti-microRNA-325-3p group,the MPP++microRNA-325-3p+pcDNA-calcineurin/TFEB group showed higher levels of calcineurin,apoptosis rate,MDA,CYC,P62,GRP78,and LC3-Ⅱ/LC3-Ⅰ,and lower levels of TFEB,microRNA-325-3p,and GSH(P＜0.05).Conclusion:MicroRNA-325-3p interferes with the calcineurin/TFEB pathway to alleviate cellular oxidative stress,inhibit neuronal apoptosis,enhance cellular autophagy,and improve endoplasmic reticulum stress and damage in the cell model of Parkinson's disease.This may represent a potential molecular target for the treatment of Parkinson's disease and provide a relevant theoretical basis for the diagnosis and treatment of Parkinson's disease.
班维固;卿鹏;滕秀英;陆丽娜;朱莹;齐辉
黑龙江中医药大学附属第二医院,哈尔滨,150000暨南大学附属第一医院,广州,510000黑龙江中医药大学附属第二医院,哈尔滨,150000黑龙江中医药大学,哈尔滨,150000黑龙江中医药大学附属第二医院,哈尔滨,150000黑龙江中医药大学附属第二医院,哈尔滨,150000
医药卫生
钙调磷酸酶/转录因子EB微小核糖核酸-325-3p神经元凋亡帕金森病细胞模型谷胱甘肽丙二醛
Calcineurin/TFEB pathwayMicroRNA-325-3pNeuron apoptosisParkinson's disease cell modelGlutathioneMalondialdehyde
《世界中医药》 2026 (12)
2198-2203,6
国家自然科学基金面上项目(21973926)黑龙江中医药管理局面上项目(ZHY2023-104).
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