Zhang Duobin, Pan Ning, Jiang Chuan, Hao Maolin
Department of Neurology, No.1 People's Hospital, Wuhu, Anhui, China.
Department of Neurology, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
J Leukoc Biol. 2022 May;111(5):953-966. doi: 10.1002/JLB.1A0421-217RR. Epub 2021 Sep 29.
Ischemic stroke (IS) can cause disability and death, and microglia as the immune component of the CNS can release inflammatory factors and participate in blood-brain barrier (BBB) dysfunction. This study aimed to investigate the effects of long noncoding RNA (lncRNA) SNHG8 on microglia activation and BBB permeability in IS. A rat model of permanent middle cerebral artery occlusion (p-MCAO) and a cell model of oxygen and glucose deprivation (OGD) in microglia were established, followed by evaluation of neurobehavioral function, BBB permeability, brain edema, and pathologic changes of microglia in brain tissue. The activation status of microglia and expressions of inflammatory factors were detected. Cell viability and integrity of microglia membrane were assessed. The downstream microRNA (miR), gene, and pathway of SNHG8 were analyzed. LncRNA SNHG8 was down-regulated in MCAO rats. Overexpression of SNHG8 improved the neural function defect, reduced brain water content, BBB permeability, brain tissue damage and inflammation, and inhibited microglia activation. In OGD-induced microglia, overexpression of SNHG8 or miR-449c-5p down-regulation increased cell viability and decreased lactate dehydrogenase activity. Moreover, SNHG8 sponged miR-449c-5p to regulate SIRT1. Overexpression of SNHG8 increased the expression of SIRT1 and FoxO1. MiR-449c-5p mimic could annul the effect of SNHG8 overexpression on ischemic microglia. Collectively, SNHG8 inhibits microglia activation and BBB permeability via the miR-449c-5p/SIRT1/FoxO1 pathway, thus eliciting protective effects on ischemic brain injury.
缺血性中风（IS）可导致残疾和死亡，而小胶质细胞作为中枢神经系统的免疫成分，可释放炎症因子并参与血脑屏障（BBB）功能障碍。本研究旨在探讨长链非编码RNA（lncRNA）SNHG8对IS中小胶质细胞活化和血脑屏障通透性的影响。建立了大鼠永久性大脑中动脉闭塞（p-MCAO）模型和小胶质细胞氧糖剥夺（OGD）细胞模型，随后评估神经行为功能、血脑屏障通透性、脑水肿以及脑组织中小胶质细胞的病理变化。检测了小胶质细胞的活化状态和炎症因子的表达。评估了小胶质细胞的活力和细胞膜完整性。分析了SNHG8的下游微小RNA（miR）、基因和信号通路。lncRNA SNHG8在MCAO大鼠中表达下调。SNHG8的过表达改善了神经功能缺损，降低了脑含水量、血脑屏障通透性、脑组织损伤和炎症反应，并抑制了小胶质细胞活化。在OGD诱导的小胶质细胞中，SNHG8的过表达或miR-449c-5p的下调增加了细胞活力并降低了乳酸脱氢酶活性。此外，SNHG8吸附miR-449c-5p以调节SIRT1。SNHG8的过表达增加了SIRT1和FoxO1的表达。miR-449c-5p模拟物可消除SNHG8过表达对缺血性小胶质细胞的影响。总体而言，SNHG8通过miR-449c-5p/SIRT1/FoxO1信号通路抑制小胶质细胞活化和血脑屏障通透性，从而对缺血性脑损伤产生保护作用。
