miR-125b-5p对创伤性脑损伤诱发大鼠认知功能障碍的干预作用及其机制*

doi:10.12047/j.cjap.6313.2022.079

摘要/Abstract

摘要： 目的: 研究miR-125b-5p对创伤性脑损伤(TBI)引起的大鼠认知功能障碍的影响及其分子机制。方法: 将大鼠随机分为Control组、TBI组(模型组)、NC agomir组(假阴性组)、miR-125b-5p agomir组(高表达组),每组5只。假阴性组和高表达组分别脑室注射NC agomir和miR-125b-5p agomir,除Control组外各组均用改良Feeney法建立脑损伤模型。通过行为学实验对大鼠的运动协调、学习记忆、神经损伤程度等进行评估。通过ELISA和Western blot对各组大鼠海马组织中miR-125b-5p、炎性因子,以及神经相关因子的表达水平进行检测。最后使用生物信息学结合RT-PCR和Western blot对miR-125b-5p的下游靶基因进行预测和验证。结果: 与对照组相比,模型组和假阴性组大鼠miR-125b-5p的表达水平显著下调、mNSS 评分显著升高、运动协调能力及学习记忆能力显著下降、白介素(IL-1β、IL-6)及肿瘤坏死因子(TNF-α)表达水平显著升高、BDNF和NGF的表达水平显著下降、GFAP的表达水平显著升高(P＜0.01);与模型组和假阴性组相比,高表达组大鼠的miR-125b-5p的表达水平显著升高、mNSS 评分显著降低、运动协调能力及学习记忆能力明显增高、IL-1β、IL-6及TNF-α表达水平显著下降、BDNF及NGF的表达水平升高、GFAP的表达水平显著下降(P＜0.01)。生信分析显示,MMP-15为miR-125b-5p的下游靶标基因,与对照组相比,模型组和假阴性组MMP-15表达显著升高(P＜0.01);与模型组和假阴性组相比,高表达组MMP-15的表达显著降低(P＜0.01)。结论: miR-125b-5p可改善TBI引起的大鼠认知功能障碍,这可能与其调控MMP-15的表达水平,进而抑制TBI后神经炎症反应,促进神经元再生相关。

关键词: 大鼠, miR-125b-5p, MMP-15, 认知功能障碍, 创伤性脑损伤, 炎症因子

Abstract: Objective: To investigate the effects and molecular mechanisms of miR-125b-5p on cognitive dysfunction caused by traumatic brain injury (TBI). Methods: The rats were randomly divided into control group, TBI group (model group), NC Agomir group (false negative group) and miR-125b-5p agomir group (high expression group), with 5 rats in each group. The false negative group and the high expression group were injected with NC agomir and miR-125b-5p agomir, respectively. The brain injury model was established by modified Feeney method except control group. Animal behavioral experiments were utilized for evaluation of the motor coordination, learning and memory and the degree of nerve damage in rats; and enzyme-linked immunosorbent assays (ELISA) and Western blot (WB) were used for determination of the expression levels of inflammatory factors and nerve-related factors in the hippocampus of rats in each group respectively. Finally, combined with bioinformatics, downstream target genes of miR-125b-5p were predicted and verified by reverse transcription polymerase chain reaction (RT-PCR) and WB. Results: Compared with control group, mir-125b-5p expression level, motor coordination ability, learning and memory ability, brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) expression levels of rats in model group and false negative group were decreased significantly, the MNSS score, the expressions of interleukins (IL-1β, IL 6), tumor necrosis factor-α(TNF-α) and glial fibrillary acid protein(GFAF) were increased significantly (P＜0.01);However, compared with model group and false negative group, the above situation of rats in high expression group was opposite (P＜0.01). Bioassay showed that MMP-15 was the downstream target gene of miR-125b-5p. Compared with the control group, the expression of MMP-15 in model group and false negative group was increased significantly (P＜0.01);Compared with model group and false negative group, the expression of MMP-15 in high expression group was decreased significantly (P＜0.01) . Conclusion: miR-125b-5p can improve cognitive dysfunction induced by TBI in rats, which may be related to regulating the expression level of MMP-15, thereby inhibiting the neuroinflammatory response after TBI and promoting neuronal regeneration.

Key words: rat, miR-125b-5p, MMP-15, cognitive dysfunction, traumatic brain injury (TBI), inflammatory factors

中图分类号:

R651.1+5

王勇, 赵伟, 姜正林, 陈振华, 张欢. miR-125b-5p对创伤性脑损伤诱发大鼠认知功能障碍的干预作用及其机制^*[J]. 中国应用生理学杂志, 2022, 38(5): 424-429.

WANG Yong, ZHAO Wei, JIANG Zheng-lin, CHEN Zhen-hua, ZHANG Huan. Intervention effects of miR-125b-5p on cognitive dysfunction induced by traumatic brain injury in rats and its mechanisms[J]. CJAP, 2022, 38(5): 424-429.

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miR-125b-5p对创伤性脑损伤诱发大鼠认知功能障碍的干预作用及其机制^*

Intervention effects of miR-125b-5p on cognitive dysfunction induced by traumatic brain injury in rats and its mechanisms

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