Abstract

Purpose

Post-stroke cognitive impairment (PSCI) is a series of syndromes that meets the diagnostic criteria of cognitive impairment within 6 months after the clinical event of stroke. With the unpleasing treatment at present, this study aimed to investigate the role of microRNA (miR)-135b-5p in regulating mineralocorticoid receptor (NR3C2) in PSCI.

Methods

The rats were modeled via middle cerebral artery occlusion, and injected with miR-135b-5p agomir or antagomir to figure its role in post-stroke neurological deficits, neuronal injury, neuronal cell apoptosis, and inflammation via Behavioral tests, Nissl’s staining, flow cytometry, and TUNEL staining. The expression of miR-135b-5p and NR3C2 in rats was detected by RT-qPCR and western blot analysis. The targeting relationship between miR-135b-5p and NR3C2 was verified by dual luciferase reporter gene assay.

Results

Highly expressed miR-135b-5p relieved post-stroke neurological deficits, focal cerebral ischemia-reperfusion (FCIR) neuron injury, and reduced neuronal apoptosis and inflammatory response after FCIR in PSCI rats. Poorly expressed miR-135b-5p and highly expressed NR3C2 were present in FCIR injury in PSCI rats. miR-135b-5p can direct target NR3C2 3’UTR.

Conclusion

The study highlights that up regulation of miR-135b-5p can reduce neuronal injury and inflammatory response in PSCI by targeting NR3C2, which might be helpful for PSCI treatment.

中文翻译：

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升高的 microRNA-135b-5p 通过靶向 NR3C2 缓解中风后认知障碍的神经元损伤和炎症

摘要

目的

脑卒中后认知障碍（Post-strokecognitive damage，PSCI）是脑卒中临床事件发生后6个月内符合认知障碍诊断标准的一系列综合征。在目前治疗效果不佳的情况下，本研究旨在探讨 microRNA (miR)-135b-5p 在调节 PSCI 盐皮质激素受体 (NR3C2) 中的作用。

方法

通过大脑中动脉闭塞对大鼠进行建模，并注射 miR-135b-5p agomir 或 antagomir，通过行为测试、Nissl 染色、流式细胞术确定其在中风后神经功能缺损、神经元损伤、神经元细胞凋亡和炎症中的作用, 和 TUNEL 染色。通过RT-qPCR和western blot分析检测大鼠体内miR-135b-5p和NR3C2的表达。miR-135b-5p与NR3C2的靶向关系通过双荧光素酶报告基因检测得到验证。

结果

高表达的 miR-135b-5p 可缓解 PSCI 大鼠中风后神经功能缺损、局灶性脑缺血再灌注 (FCIR) 神经元损伤，并减少 FCIR 后的神经元凋亡和炎症反应。PSCI 大鼠的 FCIR 损伤中存在低表达的 miR-135b-5p 和高表达的 NR3C2。miR-135b-5p 可以直接靶向 NR3C2 3'UTR。

结论

该研究强调，上调 miR-135b-5p 可以通过靶向 NR3C2 减少 PSCI 中的神经元损伤和炎症反应，这可能有助于 PSCI 治疗。