Department of Neurology, The Affiliated Changsha Central Hospital, University of South China, Hunan, China.
Department of Science and Education, The Affiliated Changsha Central Hospital, University of South China, Hunan, China.
Gen Physiol Biophys. 2024 Nov;43(6):567-576. doi: 10.4149/gpb_2024035.
The present study aimed to explore the expression and molecular mechanisms of lncRNA SIX3OS1 in post-stroke cognitive impairment (PSCI). Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were applied to establish an in vitro and in vivo model of PSCI. RT-qPCR was conducted to examine the mRNA levels of SIX3OS1, miR-511-3p, and RBP4. Morris water maze test was used to evaluate spatial learning and memory ability. Cell viability and apoptosis were examined by CCK-8 and flow cytometry. The secretion level of inflammatory factors was analyzed by ELISA. DLR and RIP assay were performed to validate the target relationship. In MCAO rats and OGD/R-induced cells, SIX3OS1 and RBP4 levels were significantly elevated, while miR-511-3p was reduced. miR-511-3p targets SIX3OS1 and RBP4. Compared with the sham, the spatial learning and memory ability of MCAO rats were decreased, but the silencing of SIX3OS1 could restore them, but this restoration was partially impaired by lowing of miR-511-3p. Silencing of SIX3OS1 enhanced OGD/R-induced SH-SY5Y cell viability and inhibited apoptosis and inflammatory factor secretion, but they were both attenuated by the lowing of miR-511-3p. Silencing of SIX3OS1 can protect PSCI via targeting miR-511-3p to promote cell viability and inhibit apoptosis and inflammation.
本研究旨在探讨长链非编码 RNA SIX3OS1 在卒中后认知障碍（PSCI）中的表达及分子机制。应用大脑中动脉闭塞（MCAO）和氧葡萄糖剥夺/复氧（OGD/R）建立 PSCI 的体外和体内模型。通过 RT-qPCR 检测 SIX3OS1、miR-511-3p 和 RBP4 的 mRNA 水平。Morris 水迷宫试验用于评估空间学习和记忆能力。通过 CCK-8 和流式细胞术检测细胞活力和细胞凋亡。通过 ELISA 分析炎症因子的分泌水平。通过 DLR 和 RIP 测定验证靶标关系。在 MCAO 大鼠和 OGD/R 诱导的细胞中，SIX3OS1 和 RBP4 水平显著升高，而 miR-511-3p 降低。miR-511-3p 靶向 SIX3OS1 和 RBP4。与假手术组相比，MCAO 大鼠的空间学习和记忆能力下降，但 SIX3OS1 的沉默可以恢复它们，但 miR-511-3p 的降低部分损害了它们的恢复。SIX3OS1 的沉默增强了 OGD/R 诱导的 SH-SY5Y 细胞活力，抑制了细胞凋亡和炎症因子的分泌，但 miR-511-3p 的降低削弱了它们。沉默 SIX3OS1 可以通过靶向 miR-511-3p 促进细胞活力、抑制细胞凋亡和炎症来保护 PSCI。
