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骨髓间充质干细胞对急性脊髓损伤大鼠神经功能的保护机制研究

Neuroprotective mechanism of bone marrow mesenchymal stem cells in acute spinal cord injury in rats

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【作者】 肖雨瑶; 刘千寻; 周若琦; 朱可馨; 李双月;

【Author】 XIAO Yuyao;LIU Qianxun;ZHOU Ruoqi;ZHU Kexin;LI Shuangyue;College of Traditional Chinese Medicine, Beijing University of Chinese Medicine;Queen Mary School, Nanchang University;School of Public Health, Dalian Medical University;

【通讯作者】 李双月;

【机构】 北京中医药大学中医学院; 南昌大学玛丽女王学院; 大连医科大学公共卫生学院;

【摘要】 目的 探索骨髓间充质干细胞(BMSCs)对急性脊髓损伤(ASCI)大鼠神经功能的保护作用及机制。方法 将39只雄性SD大鼠随机分为假手术组(Sham组)、ASCI组和BMSCs组。Sham组只切除椎板;ASCI组进行胸10椎板切除+脊髓损伤;BMSCs组在ASCI组基础上行BMSCs移植。术后1、4、7天,采用运动及感觉功能(Reuter)评分和巴索-比蒂-布雷斯纳汉(BBB)评分对大鼠神经功能进行评估。术后第7天,HE染色观察大鼠受损脊髓组织形态学变化,生化法检测大鼠脊髓组织中Fe2+、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)含量,采用Western blot法检测谷胱甘肽过氧化物酶4(GPX4)和胱氨酸/谷氨酸反向转运蛋白(xCT)的表达水平。结果术后1天,BMSCs组和ASCI组大鼠出现运动和感觉功能障碍;术后7天,BMSCs组大鼠Reuter评分明显低于ASCI组[(4.00±0.47)分vs(7.10±0.32)分];BBB评分明显高于ASCI组[(6.70±0.67)分vs(4.00±0.67)分],差异均有统计学意义(P<0.05)。HE染色结果显示,ASCI组大鼠胸10节段脊髓灰质内部分神经元肿胀、细胞质淡染,部分皱缩致周边出现空隙,神经元突起减少;白质内可见神经细胞溶解形成的大量空泡,横行神经纤维减少。BMSCs组大鼠脊髓灰质区神经元肿胀或皱缩数量减少,神经元突起增多;白质区空泡减少,横行粗大神经纤维增多。与Sham组相比,ASCI组大鼠脊髓组织Fe2+、MDA含量明显升高,SOD活性及GSH含量明显降低;BMSCs组较ASCI组Fe2+和MDA含量降低,SOD活性及GSH含量升高,差异均有统计学意义(P<0.05)。此外,与Sham组相比,ASCI组大鼠受损脊髓组织中的GPX4和xCT蛋白水平降低,BMSCs组较ASCI组GPX4和xCT蛋白水平升高,差异均有统计学意义(P<0.05)。结论BMSCs对ASCI大鼠神经功能具有保护作用,铁死亡相关机制可能参与其中。

【Abstract】 Objective To explore the neuroprotective effects and underlying mechanisms of bone marrow stromal cells(BMSCs) in rat acute spinal cord injury(ASCI). Methods A total of 39 male SD rats were randomly assigned to three groups:sham, ASCI and BMSCs. The Sham group underwent only laminectomy; ASCI group underwent laminectomy and spinal cord injury; BMSCs group received BMSCs transplantation following ASCI. On the 1st, 4th, 7th day after surgery, the neurological function was evaluated using the Reuter score and BBB score. On the 7th day, HE staining was performed to assess spinal cord morphology. Levels of Fe2+, MDA, SOD, and GSH in the spinal cord tissue of rats were detected using commercial assay kits.Protein expression of GPX4 and xCT was detected using Western blot. Results On the 1st day after surgery, both ASCI and BMSCs groups showed motor and sensory dysfunction. On the 7th day, the ASCI group showed significantly higher Reuter scores[( 7.10±0.32) points vs(4.00±0.47) points ]and lower BBB scores[( 4.00±0.67) points vs(6.70±0.67) points ]compared to the BMSCs group(P<0.05). HE staining revealed that, in the ASCI group, the gray matter showed some neurons swollen or shrunken, cytoplasmic pallor, reduced synapses; the white matter showed a large number of vacuoles and a decrease in transverse nerve fibers. In contrast, the BMSCs group showed reduced neuronal damage, increased synaptic in the gray matter;and fewer vacuoles with more transverse fibers in white matter. ASCI group showed increased Fe2+ and MDA contents and decreased SOD and GSH contents compared to the sham group(P< 0.05). BMSCs treatment significantly reversed these changes. In addition, expression levels of GPX4 and xCT significantly increased in the BMSCs group compared to the ASCI group(P<0.05). Conclusion Ferroptosis might be involved in the neuroprotective mechanism of BMSCs in acute spinal cord injury.

  • 【文献出处】 大连医科大学学报 ,Journal of Dalian Medical University , 编辑部邮箱 ,2025年03期
  • 【分类号】R651.2
  • 【下载频次】19
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