Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, P.R. China.
Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University, Changsha 410003, Hunan, P.R. China.
Aging (Albany NY). 2020 Jun 7;12(11):10931-10950. doi: 10.18632/aging.103307.
Microglial cells are the first line immune cells that initiate inflammatory responses following cerebral ischemia/reperfusion(I/R) injury. Microglial cells are also associated with a novel subtype of pro-inflammatory programmed cell death known as pyroptosis. Research has been directed at developing treatments that modulate inflammatory responses and protect against cell death caused by cerebral I/R. Key among such treatments include mesenchymal stem cell (MSC) therapy. A unique type of MSC termed olfactory mucosa mesenchymal stem cell (OM-MSC) confers neuroprotection by promoting the secretion of paracrine factors, and neuroprotection. This study investigated whether hypoxic OM-MSCs could inhibit microglial cell death upon I/R insult in . A traditional oxygen-glucose deprivation/reperfusion (OGD/R) model, analogous to I/R, was established. Results showed that OGD/R induced apoptosis and pyroptosis in microglial cells while hypoxia in OM-MSCs significantly attenuated these effects. Moreover, the effects of OM-MSCs were mediated by Hypoxia-inducible factor 1-alpha (HIF-1α). Taken together, these findings reveal that hypoxia-preconditioned OM-MSC inhibits pyroptotic and apoptotic death of microglial cell in response to cerebral ischemia/reperfusion insult by activating HIF-1α in .
小胶质细胞是在脑缺血/再灌注（I/R）损伤后引发炎症反应的第一道免疫细胞。小胶质细胞也与一种新型的促炎程序性细胞死亡有关，称为细胞焦亡。研究旨在开发调节炎症反应和防止脑 I/R 引起的细胞死亡的治疗方法。其中关键的治疗方法包括间充质干细胞（MSC）治疗。一种称为嗅黏膜间充质干细胞（OM-MSC）的独特 MSC 类型通过促进旁分泌因子的分泌和神经保护来发挥神经保护作用。本研究探讨了低氧 OM-MSC 是否可以抑制 I/R 损伤后 中的小胶质细胞死亡。建立了类似于 I/R 的传统氧葡萄糖剥夺/再灌注（OGD/R）模型。结果表明，OGD/R 诱导小胶质细胞凋亡和细胞焦亡，而 OM-MSCs 的低氧显著减弱了这些作用。此外，OM-MSCs 的作用是由缺氧诱导因子 1-α（HIF-1α）介导的。总之，这些发现表明，低氧预处理的 OM-MSC 通过在 中激活 HIF-1α，抑制脑缺血/再灌注损伤后小胶质细胞的细胞焦亡和凋亡性死亡。
