He Jialin, Liu Jianyang, Huang Yan, Zhuo Yi, Chen Wei, Duan Da, Tang Xiangqi, Lu Ming, Hu Zhiping
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
Front Cell Dev Biol. 2020 Oct 30;8:586541. doi: 10.3389/fcell.2020.586541. eCollection 2020.
Olfactory mucosa mesenchymal stem cells (OM-MSCs) have exhibited their effectiveness in central nervous system diseases and provided an appealing candidate for the treatment of ischemic stroke. Previous evidence have shown that Golgi apparatus (GA) secretory pathway Ca-ATPase isoform1 (SPCA1) was a potential therapeutic target for ischemic stroke. In this study, we explored the neuroprotective mechanism of OM-MSCs and its effect on the expression and function of SPCA1 during cerebral ischemia/reperfusion. Based on and experiments, we discovered that OM-MSCs attenuated apoptosis and oxidative stress in ischemic stroke models, reduced the cerebral infarction volume, and improved the neurologic deficits of rats. OM-MSCs also upregulated SPCA1 expression and alleviated Ca overload and decreased the edema and dissolution of the GA in neurons. Moreover, we discovered that SPCA1 depletion in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated N2a cells mitigated the protective effects of OM-MSCs. Altogether, OM-MSCs exerted neuroprotective effects in ischemic stroke probably modulating SPCA1 and reducing the edema and dissolution of the GA in neurons.
嗅黏膜间充质干细胞(OM-MSCs)已在中枢神经系统疾病中展现出其有效性,并为缺血性中风的治疗提供了一个有吸引力的候选方案。先前的证据表明,高尔基体(GA)分泌途径钙ATP酶同工型1(SPCA1)是缺血性中风的一个潜在治疗靶点。在本研究中,我们探讨了OM-MSCs的神经保护机制及其在脑缺血/再灌注期间对SPCA1表达和功能的影响。基于[具体实验1]和[具体实验2]实验,我们发现OM-MSCs减轻了缺血性中风模型中的细胞凋亡和氧化应激,减小了脑梗死体积,并改善了大鼠的神经功能缺损。OM-MSCs还上调了SPCA1表达,减轻了钙超载,并减少了神经元中GA的水肿和溶解。此外,我们发现,在氧糖剥夺/复氧(OGD/R)处理的N2a细胞中敲低SPCA1会减弱OM-MSCs的保护作用。总之,OM-MSCs可能通过调节SPCA1并减少神经元中GA的水肿和溶解,在缺血性中风中发挥神经保护作用。