高表达 microRNA-135b-5p 通过靶向 NR3C2 减轻卒中后认知障碍中的神经元损伤和炎症。
Elevated microRNA-135b-5p relieves neuronal injury and inflammation in post-stroke cognitive impairment by targeting NR3C2.
机构信息
Department of Emergency, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, P.R. China.
Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, P.R. China.
出版信息
Int J Neurosci. 2022 Jan;132(1):58-66. doi: 10.1080/00207454.2020.1802265. Epub 2020 Aug 4.
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 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.
目的
卒中后认知障碍（PSCI）是一系列综合征，其在卒中临床事件后 6 个月内符合认知障碍的诊断标准。鉴于目前不理想的治疗方法，本研究旨在探讨微小 RNA（miR）-135b-5p 在调节 PSCI 中盐皮质激素受体（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 激动剂或拮抗剂，以研究其在卒中后神经功能缺损、神经元损伤、神经元细胞凋亡和炎症中的作用。采用行为学测试、尼氏染色、流式细胞术和 TUNEL 染色检测大鼠的神经功能缺损、神经损伤、神经元细胞凋亡和炎症。采用 RT-qPCR 和 Western blot 分析检测大鼠 miR-135b-5p 和 NR3C2 的表达。采用双荧光素酶报告基因检测验证 miR-135b-5p 与 NR3C2 的靶向关系。
结果
高表达 miR-135b-5p 可减轻 PSCI 大鼠卒中后神经功能缺损、局灶性脑缺血再灌注（FCIR）神经元损伤，并减少 FCIR 后神经元凋亡和炎症反应。PSCI 大鼠 FCIR 损伤中存在低表达 miR-135b-5p 和高表达 NR3C2。miR-135b-5p 可直接靶向 NR3C2 3'UTR。
结论
本研究强调，通过靶向 NR3C2，上调 miR-135b-5p 可减轻 PSCI 中的神经元损伤和炎症反应，这可能有助于 PSCI 的治疗。
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