Background: Subarachnoid hemorrhage (SAH) is a cerebral hemorrhage disease that severely damages the brain and causes cognitive impairment (CI). Therefore, accurate and appropriate treatment strategies are urgently needed. The application of nimodipine can not only improve blood circulation in patients with SAH but also repair ischemic neuron injury.
Purpose: To investigate the effects of nimodipine and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-27a/microtubule-associated protein tau (MAPT) axis on CI after SAH.
Methods: One hundred and twenty healthy male rats were selected and equally divided into control group, sham operation group, model group, PBS group, nimodipine group (drug group), NC siRNA group, NC mimics group, NEAT1 siRNA, miR-27a mimics, MAPT siRNA, drug + NEAT1-ad, and drug + NC-ad groups by random number table. Rats in the model group were constructed by double-hemorrhage model, and expression vectors were injected into the tail to regulate the expression of lncRNA NEAT1, miR-27a and MAPT. In addition, Western blot was employed to detect brain tissue protein, flow cytometry was applied to measure brain tissue apoptosis, and MTT was utilized to determine cell activity, so as to evaluate brain damage and cognitive function in each group.
Results: Nimodipine, down-regulated lncRNA NEAT1, up-regulated miR-27a and down-regulated MAPT all improved brain damage and CI, inhibited brain tissue cell apoptosis, and enhanced brain cell activity. The common binding sites of lncRNA NEAT1 and MAPT were found on the miR-27a sequence fragment, and miR-27a could be paired with the former two. Nimodipine was found to cause the down-regulation of lncRNA NEAT1 and MAPT, as well as the up-regulation of miR-27a.
Conclusion: Nimodipine can improve CI after SAH in rats through the lncRNA NEAT1/miR-27a/MAPT axis.



中文翻译：

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尼莫地平通过 IncRNA NEAT1/miR-27a/MAPT Axis 改善大鼠蛛网膜下腔出血后的认知障碍。

背景：蛛网膜下腔出血（SAH）是一种严重损害大脑并导致认知障碍（CI）的脑出血疾病。因此，迫切需要准确和适当的治疗策略。尼莫地平的应用不仅可以改善SAH患者的血液循环，还可以修复缺血性神经元损伤。
目的：研究尼莫地平和 lncRNA 核副啄木鸟组装转录物 1 (NEAT1)/miR-27a/微管相关蛋白 tau (MAPT) 轴对 SAH 后 CI 的影响。
方法：选取健康雄性大鼠120只，平均分为对照组、假手术组、模型组、PBS组、尼莫地平组（药物组）、NC siRNA组、NC模拟组、NEAT1 siRNA、miR-27a模拟组、MAPT siRNA、药物 + NEAT1-ad 和药物 + NC-ad 组的随机数字表。模型组大鼠采用双出血模型构建，尾部注射表达载体调节lncRNA NEAT1、miR-27a和MAPT的表达。此外，采用Western blot检测脑组织蛋白，流式细胞仪检测脑组织凋亡，MTT检测细胞活性，评价各组脑损伤和认知功能。
结果：尼莫地平、下调的lncRNA NEAT1、上调的miR-27a和下调的MAPT均能改善脑损伤和CI，抑制脑组织细胞凋亡，增强脑细胞活性。在 miR-27a 序列片段上发现了 lncRNA NEAT1 和 MAPT 的共同结合位点，miR-27a 可以与前两者配对。尼莫地平被发现导致 lncRNA NEAT1 和 MAPT 的下调，以及 miR-27a 的上调。
结论：尼莫地平可通过lncRNA NEAT1/miR-27a/MAPT轴改善大鼠SAH后CI。