Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China.
Metab Brain Dis. 2023 Oct;38(7):2327-2338. doi: 10.1007/s11011-023-01273-9. Epub 2023 Aug 12.
This report aimed to explore whether miR-188-5p regulated the pathological regulatory network of cerebral ischemia/reperfusion (I/R) injury. We simulated the cerebral I/R injury model with MACO/R and OGD/R treatments. Neuronal viability and apoptosis were assessed. The contents of miR-188-5p and Lin 28a were evaluated. The abundances of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured. The interaction of miR-188-5p and Lin28a was confirmed. Lin28a silencing was supplemented to determine the delicate regulation of miR-188-5p. We revealed that miR-188-5p was upregulated and Lin28a was downregulated in I/R rats and OGD/R-induced cells. miR-188-5p silencing remarkably reduced the cerebral infarction volume, neurobehavioral score, brain edema, and Evans blue leakage. miR-188-5p silencing enhanced neuronal viability and alleviated apoptosis. The abundance of Bax and cleaved caspase-3 was reduced by miR-188-5p silencing, while Bcl-2 was augmented. miR-188-5p silencing impeded the contents of TNF-α, IL-1β, and IL-6. miR-188-5p interacted with Lin28a and negatively regulated its expression. Interestingly, extra Lin28a silencing reversed apoptosis and the content of inflammatory cytokines. Our studies confirmed that miR-188-5p silencing alleviated neuronal apoptosis and inflammation by mediating the expression of Lin28a. The crosstalk of miR-188-5p and Lin28a offered a different direction for ischemic stroke therapy.
本报告旨在探讨 miR-188-5p 是否调控脑缺血/再灌注（I/R）损伤的病理调控网络。我们用 MACO/R 和 OGD/R 处理模拟脑 I/R 损伤模型。评估神经元活力和细胞凋亡。评估 miR-188-5p 和 Lin28a 的含量。测量凋亡相关蛋白（Bax、Bcl-2 和 cleaved caspase-3）和促炎细胞因子（TNF-α、IL-1β 和 IL-6）的含量。证实 miR-188-5p 和 Lin28a 的相互作用。补充 Lin28a 沉默以确定 miR-188-5p 的精细调控。我们揭示 miR-188-5p 在 I/R 大鼠和 OGD/R 诱导的细胞中上调，Lin28a 下调。miR-188-5p 沉默显著减少脑梗死体积、神经行为评分、脑水肿和 Evans 蓝漏出。miR-188-5p 沉默增强神经元活力并减轻细胞凋亡。Bax 和 cleaved caspase-3 的丰度通过 miR-188-5p 沉默减少，而 Bcl-2 增加。miR-188-5p 沉默阻碍 TNF-α、IL-1β 和 IL-6 的含量。miR-188-5p 与 Lin28a 相互作用并负调控其表达。有趣的是，额外的 Lin28a 沉默逆转了细胞凋亡和炎症细胞因子的含量。我们的研究证实，miR-188-5p 沉默通过调节 Lin28a 的表达来减轻神经元凋亡和炎症。miR-188-5p 和 Lin28a 的串扰为缺血性中风治疗提供了一个不同的方向。
