| 冯思宁,王帅,孙师,苏浩,张立新.经颅磁刺激联合骨髓间充质干细胞移植治疗对脊髓损伤大鼠功能恢复的作用机制[J].中国康复,2022,37(2):67-74 |
| 经颅磁刺激联合骨髓间充质干细胞移植治疗对脊髓损伤大鼠功能恢复的作用机制 |
| Mechanism of transcrianal magnetic stimulation combined with bone marrow mesenchymal stem cells transplantation therapy for function recovery in rats with spinal cord injury |
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| DOI： |
| 中文关键词: 脊髓损伤 经颅磁刺激 骨髓间充质干细胞 功能恢复 |
| 英文关键词: Spinal cord injury Transcranial magnetic stimulation Bone marrow mesenchymal stem cells Functional recovery |
| 基金项目:国家自然科学青年基金项目（81101462）；辽宁省自然科学基金项目(201602875)；辽宁省公益科学基金项目(2016003001)；辽宁省自然科学基金项目(20180551013)；辽宁省重点大学基础研究项目（LQNK201712） |
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| 中文摘要: |
| 目的：观察经颅磁刺激（TMS）联合骨髓间充质干细胞（BMSCs）治疗对脊髓损伤（SCI）大鼠运动功能的影响，初步探讨其作用机制。方法：8周龄清洁级SD大鼠60只，随机分成对照组、模型组、BMSCs组、TMS组、TMS+BMSCs组，每组12只，采用改良Allen’s法制作大鼠SCI模型。SCI后1d、14d、28d分别行BBB评分评定大鼠运动功能。取SCI 4周后大鼠损伤的脊髓标本行免疫荧光染色观察NeuN的表达，行Western blot检测，观察GFAP、GAP-43、Nogo-A蛋白的表达及分布。结果：术后4周，BMSCs组、TMS组及TMS+BMSCs联合组评分均较模型组及单一治疗组提高（P＜0.01）。BMSCs组、TMS组及TMS+BMSCs组NeuN表达均较模型组增加（P＜0.01）。BMSCs组、TMS组及TMS+BMSCs组能够上调GAP-43的表达，下调GFAP、Nogo-A的表达（P＜0.01），且TMS+BMSCs组对以上蛋白表达调节效果更为显著（P＜0.01）。结论： BMSCs、TMS及TMS+BMSCs联合治疗组能通过上调GAP-43，下调GFAP、Nogo-A改善脊髓损伤局部微环境，有利于突触形成，减少瘢痕形成，从而促进大鼠运动功能的恢复。联合治疗组效果更佳。 |
| 英文摘要: |
| Objective: To observe the effect of transcrianal magnetic stimulation (TMS) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on motor function in rats with spinal cord injury (SCI) and explore its mechanism. Methods: Totally, 60 specific-pathogen-free Sprague-Dawley rats were randomly assigned into 5 groups (12 in each group), including group A with sham operation without SCI, group B with SCI only, and group C-E with SCI and treatments of BMSCs transplantation, TMS, BMSCs transplantation combined with TMS, respectively. The SCI model was established with Allen’s method. Motor function was evaluated using BBB scale for all the rats at the day one, 14, and 28 after the SCI operation. Injured spinal cord tissue specimens were sampled at 4th week after the SCI operation for observations of NeuN expression with immunofluorescent staining and detections of GFAP, GAP-43, Nogo-A protein expression with Western blot. Results: At 4th week after the SCI operation, the rats with BMSCs transplantation, TMS and TMS combined with BMSCs transplantation had insignificantly higher BBB scale scores than in those without the treatments (P<0.01). The BBB scale scores in the rats with TMS combined with BMSCs transplantation were significantly higher than those in the rats only with SCI operation (P<0.001) and with single treatment of BMSCs transplantation (P<0.01). The expression of NeuN in BMSCs, TMS and TMS + BMSCs groups was up-regulated compared to the SCI group, and the up-regulation of NeuN was more significant in the combined treatment group. Up-regulated expression of GAP-43 and down-regulated expression of GFAP and Nogo-A in spinal cord tissues were measured in the SCI rats with the treatments of BMSCs transplantation, TMS and TMS combined with BMSCs transplantation. All the up- and down-regulated protein expression levels were more re-markable for the rats with TMS combined with BMSCs transplantation therapy. Conclusion: BMSCs transplantation, TMS and TMS combined with BMSCs transplantation treatment could up-regulate the expression of GAP-43, but down-regulate the expression of GFAP and Nogo-A in spinal cord tissues of SCI rats, which may promote neuronal synapsis formation and inhibit cicatrization of wounds through improving microenvironment and increasing neural factor secretion, finally promoting motor function in rats with SCI. The effect of combined treatment group is more satisfactory. |
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