DFO通过HIF-1α/VEGF信号通路促进脊髓损伤修复
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重庆市科卫联合医学科研项目(2019MSXM046);昆山市科技计划项目(KS18032)


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    摘要:

    目的 探讨去铁胺(DFO)对缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)表达的调控作用,以及因此对脊髓损伤修复的促进作用。〖HTH〗方法 对40只SD大鼠进行脊髓损伤造模,并随机分为4组:假手术组10只,对照组10只,DFO 30 mg/Kg腹腔注射组(DFO 30组)10只以及100 mg/Kg腹腔注射组(DFO 100组)10只。术后观察大鼠行为学功能,脊髓病理学改变以及HIF-1α/VEGF表达情况。结果 术后1周开始,DFO两组大鼠行为学功能较对照组明显改善(均P<0.05);而术后2周开始,DFO 100组大鼠行为学功能较对照组进一步明显改善,且DFO 100组改善程度优于DFO 30组(均P<0.05)。术后4周,对照组大鼠脊髓组织明显减少,内仅有少量HIF-1α/VEGF表达,而DFO 30组髓鞘残余面积相对于对照组明显恢复,DFO 100组髓鞘残余面积明显高于DFO 30组(均P<0.05);DFO 30组HIF-1α/VEGF表达量明显高于对照组,DFO 100组HIF-1α/VEGF表达量较DFO 30组更明显(均P<0.05)。结论 DFO通过调控HIF-1α/VEGF表达有效促进脊髓损伤修复,大剂量DFO应用可能具有更好的脊髓损伤修复效果。

    Abstract:

    Objective To investigate the regulatory effect of Deferoxamine (DFO) on the expression of hypoxia inducible factor1 (HIF-1)/Vascular endothelial Growth Factor (VEGF), and its promotion effect on spinal cord injury repair. Methods 40 SD rats were modeled after spinal cord injury and randomly divided into 4 groups: sham operation group (10), control group (10), DFO 30mg/Kg intraperitoneal injection group (10) and DFO 100 mg/Kg intraperitoneal injection group (10). The behavioral function and pathological changes of the spinal cord were observed after the operation, and the expression of HIF-1 /VEGF was observed. Results From one week after operation, behavioral function of DFO group and control group was significantly improved (P<0.05). However, from two weeks after the operation, the behavioral function of rats in the DFO 100 group was further significantly improved compared with the control group (P<0.01),and the degree of improvement in the DFO 100 group was better than that in the DFO 30 group (P<0.05). Four weeks after the operation, the spinal cord tissues of rats in the control group were significantly reduced, with only a small amount of HIF1/VEGF expression. The residual area of myelin sheath in the DFO 30 group was significantly restored compared with the control group (P<0.01), and the residual area of myelin sheath in the DFO 100 group was significantly higher than that in the DFO 30 group (P<0.05). The HiF1/VEGF expression in DFO 30 group was significantly higher than that in the control group (P<0.05), and the HIF-1/VEGF expression in DFO 100 group was more significant than that in DFO 30 group(P<0.05). Conclusion DFO can effectively promote spinal cord injury repair by regulating HiF-1/VEGF expression. Large dose DFO application may have a better effect on spinal cord injury repair.

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  • 在线发布日期: 2021-08-24
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