Department of Neurology, Yichun People's Hospital of Jiangxi Province, No. 1061 Jinxiu Avenue, Yuanzhou District, Yichun City, Jiangxi Province, 336000, China.
Appl Biochem Biotechnol. 2024 Aug;196(8):5235-5248. doi: 10.1007/s12010-023-04802-5. Epub 2023 Dec 28.
MiRNAs are related to neuronal proliferation and apoptosis following cerebral ischemia-reperfusion injury (CIRI). This study focused on miR-30c-5p in the disease. An oxygen-glucose deprivation/re-oxygenation (OGD/R) model was prepared in HT22 cells and transfected to overexpress miR-30c-5p and G Protein Subunit Alpha I2 (GNAI2) respectively or co-transfected to silence miR-30c-5p and GNAI2. Meanwhile, a middle cerebral artery occlusion (MCAO) model was constructed in mice, and miR-30c-5p and GNAI2 were silenced in vivo simultaneously. The mice were evaluated for neurological damage, apoptosis, and inflammation. HT22 cells were tested for cytotoxicity, proliferation, apoptosis, and inflammatory factors. The interaction between miR-30c-5p and GNAI2 was predicted, analyzed, and confirmed. MiR-30c-5p was found to be downregulated in both experimental models. miR-30c-5p reduced lactate dehydrogenase production, inflammatory response, inhibit apoptosis, and enhanced neuronal proliferation, while GNAI2 overexpression showed the opposite results. Downregulated miR-30c-5p worsened neurological function, apoptosis, and inflammation of MCAO mice while silencing GNAI2 attenuated the influence of downregulated miR-30c-5p. MiR-30c-5p can improve neuronal apoptosis and inflammatory response caused by CIRI and is neuroprotective by targeting GNAI2, providing a new target for treating CIRI.
miRNAs 与脑缺血再灌注损伤 (CIRI) 后的神经元增殖和凋亡有关。本研究聚焦于该疾病中的 miR-30c-5p。在 HT22 细胞中制备氧葡萄糖剥夺/复氧 (OGD/R) 模型,并分别转染以过表达 miR-30c-5p 和 G 蛋白亚单位 Alpha I2 (GNAI2),或共转染以沉默 miR-30c-5p 和 GNAI2。同时,构建小鼠大脑中动脉闭塞 (MCAO) 模型,并在体内同时沉默 miR-30c-5p 和 GNAI2。评估小鼠的神经损伤、凋亡和炎症。检测 HT22 细胞的细胞毒性、增殖、凋亡和炎症因子。预测、分析和验证 miR-30c-5p 与 GNAI2 之间的相互作用。在两个实验模型中均发现 miR-30c-5p 下调。miR-30c-5p 降低乳酸脱氢酶的产生、炎症反应、抑制凋亡,并增强神经元增殖,而 GNAI2 过表达则显示出相反的结果。下调的 miR-30c-5p 使 MCAO 小鼠的神经功能、凋亡和炎症恶化,而沉默 GNAI2 则减轻了下调的 miR-30c-5p 的影响。miR-30c-5p 可通过靶向 GNAI2 改善 CIRI 引起的神经元凋亡和炎症反应,具有神经保护作用,为治疗 CIRI 提供了新的靶点。