| 孙启孟,李宗明,张姣.骨髓间充质干细胞经 Nrf2/HO?1信号通路对创伤性脊髓损伤大鼠神经的保护作用[J].安徽医药,2021,25(11):2222-2227. |
| 骨髓间充质干细胞经 Nrf2/HO?1信号通路对创伤性脊髓损伤大鼠神经的保护作用 |
| Effect of bone marrow mesenchymal stem cells on neuroprotection in rats with traumatic spi? nal cord injury via Nrf2/HO-1 signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2021.11.023 |
| 中文关键词: 脊髓损伤 间质干细胞移植 神经保护 Nrf2/HO-1信号通路 |
| 英文关键词: Spinal cord injuries Mesenchymal stem cell transplantation Neuroprotection Nrf2/HO-1 signaling pathway |
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| 中文摘要: |
| 目的分析骨髓间充质干细胞( BMSCs)移植通过因子 E2相关因子 2(Nrf2)/血红素加氧酶 -1(HO-1)信号通路对脊髓损伤( SCI)大鼠神经保护作用影响。方法选取无特定病原体( SPF)级 SD雄性大鼠，分为假手术组、模型组和实验组，模型组和实验组大鼠制备 SCI模型，成功造模后实验组大鼠将 0.5 mL的 BMSCs细胞悬液( 1×107/mL)经尾静脉注射，模型组与假手术组大鼠注射等剂量 PBS溶液。观察 BMSCs细胞培养状况，各组大鼠 BBB评分、受损脊髓组织病理形态、免疫荧光染色追踪移植细胞及受损组织内 Nrf2/HO-1信号通路相关蛋白、凋亡相关蛋白等表达。结果脊髓受损后 7、14、21、28 d时实验组大鼠 BBB评分分别为( 6.27±1.44)分、(11.15±1.53)分、(14.02±1.50)分、(15.14±1.60)分，均高于模型组的( 4.73±1.35)分、(8.52±1.49)分、(9.95±1.62)分、(11.67±1.65)分( P<0.05)；模型组大鼠受损脊髓组织内 IL-6、TNF-α蛋白表达较假手术组升高，实验组大鼠受损脊髓组织内 IL-6、TNF-α蛋白表达较模型组降低，差异有统计学意义( P<0.05)；模型组大鼠受损脊髓组织内 Nfr2、NQO1、HO-1蛋白表达较假手术组升高，实验组大鼠受损脊髓组织内 Nfr2、NQO1、HO-1蛋白表达较模型组组升高，差异有统计学意义( P<0.05)；模型组大鼠受损脊髓组织内 GFAP蛋白表达较假手术组升高， NeuN蛋白表达较假手术组降低；实验组大鼠 GFAP蛋白表达比模型组下降， NeuN蛋白表达比模型组上升，差异有统计学意义( P<0.05)。结论 BMSCs移植可抑制 SCI大鼠星形胶质细胞活化和神经细胞凋亡，减轻炎症反应，加速恢复运动神经功能，其作用机制可能和 Nrf2/HO-1信号通路激活有关。 |
| 英文摘要: |
| Objective To investigate the neuroprotective effect of bone marrow mesenchymal stem cells (BMSCs) transplantation onspinal cord injury (SCI) rats through nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods SPF SD male rats were divided into sham operation group, model group and experimental group. The SCI model was prepared in the model group and the experimental group. After successful modeling, rats in the experimental group were injected with 0.5ml of BMSCs cellsuspension (1×107/ml) via tail vein. The rats in the model group and the sham-operated group were injected with an equal dose of PBS solution. The cell culture status of BMSCs was observed. The BBB scores, pathological morphology of damaged spinal cord and immunofluorescence staining of BMSCs in each group were used to track the expression of Nrf2/HO-1 signaling pathway-related proteins and apoptosis-related proteins in transplanted cells and damaged tissues.Results At the 7th, 14th, 21st and 28th day after spinal cord injury,the BBB scores of the experimental group were higher than those of the model group [(6.27±1.44),(11.15±1.53),(14.02±1.50),(15.14±1.60)vs. (4.73±1.35),(8.52±1.49),(9.95±1.62),(11.67±1.65),P<0.05]. Compared with sham group, rats in the model group had higher IL-6 and TNF levedls in the injured spinal cord tissue. The expression of α-protein was higher than that in the sham-operated group. The expression of IL-6 and TNF-α protein in the injured spinal cord of the experimental group was lower than that in the model group (P<0.05). The expressions of Nfr2, NQO1 and HO-1 protein in the injured spinal cord tissue were higher than those in the sham-operation group. The expressions of Nfr2, NQO1 and HO-1 protein in the injured spinal cord tissue of the experimental group were higher than those inthe model group. The difference was statistically significant (P<0.05); the expression of GFAP protein in injured spinal cord tissue of model group was higher than that of sham-operation group, and the expression of NeuN protein was lower than that of sham operationgroup. The expression of GFAP protein in injured spinal cord tissue of experimental group was lower than that of model group. The expression of NeuN protein was lower than that of the model group, and the difference was statistically significant(P<0.05).Conclusion BMSCs transplantation can inhibit the activation of astrocytes and neuronal apoptosis in SCI rats, reduce inflammation and acceleratethe recovery of function of nerve function. The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway. |
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