激活sigma-1受体对皮质酮诱导的星形胶质细胞线粒体损伤的影响  

Effect of sigma-1 receptor activation on corticosterone-induced mitochondrial damage in astrocytes

作　　者：汤伟栋[1] 倪静 王允 张宁 TANG Weidong;NI Jing;WANG Yun;ZHANG Ning(Department of Pharmacy,the Affiliated Hospital of Jiangsu University,Zhenjiang,Jiangsu 212001,China;Key Laboratory of New Drug Research and Clinical Pharmacy of Jiangsu Province,Xuzhou Medical University,Xuzhou,Jiangsu 221000;Hemodialysis Center,Xuzhou Ninth People′s Hospital,Xuzhou,Jiangsu 221000)

机构地区：[1]江苏大学附属医院药学部,江苏镇江212001 [2]徐州医科大学,江苏省新药研究与临床药学重点实验室,江苏徐州221000 [3]徐州市第九人民医院血液净化中心,江苏徐州221000

出　　处：《徐州医科大学学报》2025年第3期186-190,共5页Journal of Xuzhou Medical University

基　　金：江苏省自然科学基金(BK20231181)。

摘　　要：目的探讨sigma-1受体对星形胶质细胞线粒体损伤的保护作用及机制。方法构建皮质酮诱导的原代星形胶质细胞损伤模型,给予sigma-1受体特异性激动剂PRE-084进行干预,检测线粒体膜电位、三磷酸腺苷(ATP)及线粒体动力学相关蛋白表达。给予线粒体分裂抑制剂mdivi-1,观察其对sigma-1受体保护作用的影响。结果皮质酮损伤星形胶质细胞致线粒体膜电位下降、ATP产生减少,线粒体融合蛋白视神经萎缩蛋白1(OPA-1)、线粒体融合蛋白1(Mfn1)表达无明显变化,但线粒体分裂蛋白线粒体动力相关蛋白1(Drp-1)磷酸化显著降低。激活sigma-1受体可逆转损伤,表现为保护作用。给予mdivi-1后,sigma-1受体保护作用消失。结论激活sigma-1受体可保护皮质酮诱导的星形胶质细胞线粒体损伤,其机制可能与促进线粒体分裂有关。Objective To investigate the protective effect and mechanism of sigma-1 receptors on corticosteroneinduced mitochondrial damage in astrocytes.Methods A corticosterone-induced primary astrocyte damage model was established,and the sigma-1 receptor-specific agonist PRE-084 was used for intervention.Mitochondrial membrane potential,ATP production,and the expression of mitochondrial dynamics-related proteins were assessed.Furthermore,the mitochondrial fission inhibitor mdivi-1 was given to observe its effect on the protective role of sigma-1 receptors.Results Corticosterone-induced damage to astrocytes resulted in decreases in mitochondrial membrane potential and ATP production.The expression of mitochondrial fusion proteins optic atrophy 1(OPA-1)and mitochondrial fusion protein 1(Mfn1)showed no significant changes,but the phosphorylation of the mitochondrial fission protein dynamin-related protein 1(Drp-1)was significantly reduced.Activation of sigma-1 receptors reversed these damages,showing a protective effect.After treatment with mdivi-1,the protective effect of sigma-1 receptor activation was abolished.Conclusions Activation of sigma-1 receptors can protect astrocyte mitochondria from corticosterone-induced damage,which may be related to promoting mitochondrial fission.

关 键 词：sigma-1受体 星形胶质细胞 皮质酮 线粒体损伤 线粒体动力学 激动剂 

分 类 号：Q731[生物学—分子生物学]