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田明月,杨溢铎,覃琬婷,朱 晶,国海东,邵水金.雪旺细胞来源的外泌体miR-21通过靶向SPRY2促进大鼠坐骨神经损伤后修复的研究[J].中国康复医学杂志,2024,(6):767~774
雪旺细胞来源的外泌体miR-21通过靶向SPRY2促进大鼠坐骨神经损伤后修复的研究    点此下载全文
田明月  杨溢铎  覃琬婷  朱 晶  国海东  邵水金
上海中医药大学中西医结合学院人体解剖教研室,上海市,201203
基金项目:国家自然科学基金面上项目(82274633,81873357)
DOI:10.3969/j.issn.1001-1242.2024.06.002
摘要点击次数: 382
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摘要:
      摘要 目的:研究高表达miR-21的雪旺细胞(Schwann cells,SC)来源外泌体对坐骨神经损伤(sciatic nerve injury,SNI)的修复作用及机制。 方法:分别采用空载慢病毒和高表达miR-21的慢病毒感染SC株,收集SC上清外泌体并进行鉴定。采用神经断端吻合术建立SNI大鼠模型,术后随机分为模型组、SC来源外泌体组和高表达miR-21的SC来源外泌体组(n=10)。其中,SC来源外泌体组和高表达miR-21的SC来源外泌体组分别采用体外收集的外泌体局部注射进行治疗,3周后行为学实验检测神经功能恢复,免疫荧光染色评价SNI后轴突髓鞘再生,RT-qPCR检测血清外泌体miR-21及神经组织中miR-21和SPRY2的表达水平,双荧光素酶报告基因实验体外验证miR-21和SPRY2之间的靶向互作。 结果:与模型组相比,其余各组大鼠坐骨神经功能和神经再生情况均出现明显改善,RT-qPCR结果显示血清外泌体及神经组织中miR-21的表达水平显著升高,神经组织中SPRY2的表达水平显著降低,其中高表达miR-21的SC细胞来源外泌体组较SC来源外泌体组变化更显著;双荧光素酶报告基因实验表明miR-21靶向调节SPRY2的表达。结论:高表达miR-21的SC来源外泌体通过靶向SPRY2显著促进SNI后修复。
关键词:雪旺细胞  外泌体  miR-21  坐骨神经损伤  功能恢复  神经再生
Exosomal miR-21 derived from Schwann cells promoting the repair of sciatic nerve injury by targeting SPRY2    Download Fulltext
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203
Fund Project:
Abstract:
      Abstract Objective: To investigate the effect and potential mechanism of exosomal miR-21 derived from Schwann cell (SC) in the repairment of sciatic nerve injury (SNI). Method: SC was infected with negative control lentivirus and lentivirus that expression of miR-21, and its exosome was collected and identified respectively. The SNI rat model was established by nerve stump anastomosis. After surgery, the rats were randomly divided into the model group (n=10), the SC-derived exosome group (n=10) and the SC-derived exosome group (n=10) that high expression of miR-21. The SC-derived exosomes group and SC-derived exosome group that high expression of miR-21 were treated with local injection of exosome collected in vitro. After 3 weeks, the functional recovery was detected by behavioral experiment. The nerve regeneration was evaluated by immunofluorescence staining. RT-qPCR was used to detect the expression of miR-21 in serum exosome and miR-21 and SPRY2 in sciatic nerve. The targeting interaction between miR-21 and SPRY2 was verified by dual-luciferase reporter gene experiment. Result: Compared with the model group, the functional recovery and regeneration of sciatic nerve were significantly improved in the other two groups. The expression of miR-21 was significantly increased, while the expression of SPRY2 was significantly decreased. The improvement in the SC-derived exosome group with high expression of miR-21 were more significantly than those in the SC-derived exosome group. Conclusion: Exosomal miR-21 derived from SC can significantly promote the repair of sciatic nerve injury by targeting SPRY2.
Keywords:Schwann cells  exosome  miR-21  sciatic nerve injury  functional recovery  nerve regeneration
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