文章摘要
孙天宇,鲁学良,段利颖,李家驹,熊明月.MiRNA-125a-5p对于脊髓损伤后炎症反应、细胞凋亡及促进神经再生的作用机制研究[J].,2022,(6):1018-1023
MiRNA-125a-5p对于脊髓损伤后炎症反应、细胞凋亡及促进神经再生的作用机制研究
Study on the Mechanism of MiRNA-125a-5p on Inflammatory Response, Apoptosis and Nerve Regeneration after Spinal Cord Injury
投稿时间:2021-08-06  修订日期:2021-08-28
DOI:10.13241/j.cnki.pmb.2022.06.004
中文关键词: 脊髓损伤  NF-kB  MiRNA-125a-5p  炎症反应  细胞凋亡  神经再生
英文关键词: Spinal cord injury  NF-kB  MiRNA-125a-5p  Inflammatory response  Apoptosis  Nerve regeneration
基金项目:河南省科技厅基础与前沿技术研究计划项目(132300410469)
作者单位E-mail
孙天宇 河南科技大学第一附属医院新区医院骨科 河南 洛阳 471000 bluesky2123@163.com 
鲁学良 河南科技大学第一附属医院新区医院骨科 河南 洛阳 471000  
段利颖 郑州大学第五附属医院消化内科 河南 郑州 450052  
李家驹 河南科技大学第一附属医院新区医院骨科 河南 洛阳 471000  
熊明月 河南科技大学第一附属医院新区医院骨科 河南 洛阳 471000  
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中文摘要:
      摘要 目的:探讨MiRNA-125a-5p对于脊髓损伤(SCI)后炎症反应、细胞凋亡及促进神经再生的作用机制。方法:建立6周龄大鼠SCI模型,将60只大鼠随机分为对照组(n=20)、SCI组(n=20)和MiRNA-125a-5p组(n=20),对照组仅行椎板切除术,SCI组大鼠鞘内注射等量生理盐水,MiRNA-125a-5p组大鼠鞘内注射MiRNA-125a-5p agomir。采用定量实时聚合酶链反应(qRT-PCR)检测各组大鼠MiRNA-125a-5p和核因子kB(NF-kB)的相对RNA表达水平。酶联免疫吸附法(ELISA)检测炎症因子白细胞介素1(IL-1)、趋化因子受体-4(CXCR-4)和单核细胞趋化因子-1(MCP-1)水平的表达。采用蛋白免疫印迹试验检测细胞凋亡蛋白和神经调节因子蛋白的表达情况。采用Basso-Beattie-Bresnahan(BBB)运动能力评定量表评价大鼠神经运动功能。结果:与对照组比较,SCI组MiRNA-125a-5p表达均降低,NF-kB表达均升高,差异均有统计学意义(P<0.05);与SCI组比较,MiRNA-125a-5p组MiRNA-125a-5p表达均升高,NF-kB表达均降低,差异均有统计学意义(P<0.05)。与对照组比较,SCI组IL-1、CXCR-4、MCP-1水平均升高,差异有统计学意义(P<0.05)。与SCI组比较,MiRNA-125a-5p组IL-1、CXCR-4、MCP-1水平均降低,差异有统计学意义(P<0.05)。与对照组比较,SCI组半胱氨酸天冬氨酸蛋白酶3(caspase-3)、聚腺苷二磷酸-核糖聚合酶(cleaved PARP)蛋白和原癌基因(bcl-2)蛋白表达均升高,神经细胞粘附分子1(NCAM1)、神经胶质蛋白1(NL1)和神经调节蛋白-1(NRG1)蛋白表达均降低,差异有统计学意义(P<0.05);与SCI组比较,MiRNA-125a-5p组caspase-3和cleaved PARP蛋白表达均降低,bcl-2、NCAM1、NL1和NRG1蛋白表达均升高,差异均有统计学意义(P<0.05)。与对照组比较,SCI组大鼠神经运动功能评分在第7 d以后显著降低,差异有统计学意义(P<0.05);与SCI组比较,MiRNA-125a-5p组大鼠神经运动功能评分在第7 d以后均升高,差异有统计学意义(P<0.05)。结论:MiRNA-125a-5p抑制NF-kB信号通路,降低炎症反应和细胞凋亡,促进神经再生,改善大鼠神经运动功能恢复。
英文摘要:
      ABSTRACT Objective: To investigate the mechanism of MiRNA-125a-5p on inflammatory response, apoptosis and nerve regeneration after spinal cord injury (SCI). Methods: The SCI model of 6-week-old rats was established. 60 rats were randomly divided into control group (n=20), SCI group (n=20) and MiRNA-125a-5p group (n=20). Only laminectomy was performed in the control group, rats in SCI group were injected with the same amount of normal saline, and rats in MiRNA-125a-5p group were injected with MiRNA-125a-5p agomir. The relative RNA expression levels of MiRNA-125a-5p and nuclear factor kB(NF-kB) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of inflammatory factors interleukin-1(IL-1), chemokine receptor-4 (CXCR-4) and monocyte chemokine-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of apoptosis protein and neuroregulatory factor protein were detected by Western blot.Basso Beattie Bresnahan (BBB) motor ability rating scale was used to evaluate the neuromotor function of rats. Results: Compared with the control group, the expression of MiRNA-125a-5p decreased and the expression of NF-kB increased in SCI group(P<0.05); Compared with SCI group, the expression of MiRNA-125a-5p increased and the expression of NF-kB decreased in MiRNA-125a-5p group(P<0.05). Compared with the control group, the levels of IL-1, CXCR-4 and MCP-1 in SCI group were significantly higher(P<0.05). Compared with SCI group, the levels of IL-1, CXCR-4 and MCP-1 in MiRNA-125a-5p group were significantly lower (P<0.05). Compared with the control group, the expressions of caspase-3, cleaved PARP and bcl-2 protein in SCI group were increased, and the expressions of NCAM1, NL1 and NRG1 protein were decreased (P<0.05); Compared with SCI group, the expression of caspase-3 and cleaved PARP protein in MiRNA-125a-5p group decreased, and the expression of bcl-2, NCAM1, NL1 and NRG1 protein increased (P<0.05). Compared with the control group, the neuromotor function score of SCI group decreased significantly after the 7th day(P<0.05); Compared with SCI group, the neuromotor function scores of rats in MiRNA-125a-5p group increased after the 7th day, and the difference was statistically significant(P<0.05). Conclusion: MiRNA-125a-5p inhibits NF-kB signaling pathway, reduces inflammatory response and apoptosis, promotes nerve regeneration and improves the recovery of neuromotor function in rats.
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