Salem Nesrine, Salem Mohamed Y, Elmaghrabi Mohammed M, Elawady Moataz A, Elawady Mona A, Sabry Dina, Shamaa Ashraf, Elkasapy Abdel-Haleem H, Ibrhim Noha, Elamir Azza
Department of Histology and Cell Biology, Faculty of Medicine, Banha University, Banha, Egypt.
Department of Neurosurgery, Faculty of Medicine, Banha University, Banha, Egypt.
Neural Regen Res. 2017 Dec;12(12):2050-2058. doi: 10.4103/1673-5374.221163.
Methylprednisolone (MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury (SCI). Vitamin C (VC) is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells (BMMSCs), as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI (SCI induction by weight-drop method), MP (SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times), VC (SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days), MP + VC (SCI induction, followed by administration of MP and VC as the former), BMMSCs (SCI induction, followed by injection of 3 × 10 BMMSCs at the injury site), and BMMSCs + VC (SCI induction, followed by BMMSCs injection and VC administration as the former). Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.
甲基强的松龙(MP)是目前唯一被证实对急性脊髓损伤(SCI)具有神经保护作用的药物。维生素C(VC)是一种天然的水溶性抗氧化剂,通过消除对神经细胞的自由基损伤发挥神经保护作用。骨髓间充质干细胞(BMMSCs)作为多能干细胞,是SCI修复中有前景的候选者。为了评估MP、VC和BMMSCs对创伤性SCI的治疗效果,将80只成年雄性大鼠随机分为七组:对照组、SCI组(通过重物坠落法诱导SCI)、MP组(诱导SCI,随后通过尾静脉给予30mg/kg MP,每6小时一次,共五次)、VC组(诱导SCI,随后每天腹腔注射100mg/kg VC,共28天)、MP + VC组(诱导SCI,随后按前者方法给予MP和VC)、BMMSCs组(诱导SCI,随后在损伤部位注射3×10个BMMSCs)以及BMMSCs + VC组(诱导SCI,随后按前者方法注射BMMSCs并给予VC)。使用Basso小鼠评分评估运动功能恢复情况。使用苏木精-伊红染色和免疫组织化学染色评估损伤的脊髓组织。使用实时定量PCR测定转化生长因子-β、肿瘤坏死因子-α和基质金属蛋白酶-2基因的表达。与MP和/或VC相比,BMMSCs干预能更好地促进SCI大鼠神经功能的恢复,减轻神经细胞损伤,并降低转化生长因子-β、肿瘤坏死因子-α和基质金属蛋白酶-2基因的表达。更重要的是,BMMSCs与VC联合使用能诱导更明显的改善。这些结果表明,VC可增强BMMSCs对SCI的神经保护作用。