CXCL12/CXCR4对大鼠少突胶质前体细胞迁移的影响及调控

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[目的]研究CXCL12/CXCR4对大鼠少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)迁移的影响及其调控机制。[方法]通过boyden chamber小室检测不同浓度CXCL12(0 ng/ml、5 ng/ml、10 ng/ml、20 ng/ml)对大鼠OPCs迁移能力的影响,利用Western blotting实验检测相应条件下MEK1/2通路中ERK和p-ERK表达的变化;然后利用CXCR4 shRNA抑制CXCR4蛋白表达、U0126阻断MEK1/2通路,利用Western blotting实验检测相应条件下MEK1/2通路中ERK和p-ERK表达的变化,通过boyden chamber小室检测大鼠OPCs迁移能力的变化。[结果]CXCL12能够明显促进大鼠OPCs的迁移,随着胞外CXCL12浓度提高,OPCs内其特异性受体CXCR4表达逐渐增高,与0 ng/ml相比,CXCL12浓度为10 ng/ml和20 ng/ml时CXCR4蛋白相对表达明显增加,差异显著。并且明显促进MEK1/2通路蛋白ERK磷酸水平升高;抑制CXCR4蛋白表达后,CXCL12对少突胶质前体细胞迁移的促进作用受到明显抑制,并且MEK1/2通路蛋白ERK磷酸水平也受到明显抑制;用U0126阻断MEK1/2通路后,CXCL12对大鼠OPCs迁移的促进作用受到明显抑制。[结论]CXCL12/CXCR4能够通过MEK1/2通路调控大鼠OPCs的迁移,为后续深入探讨脊髓损伤治疗方法提供实验基础。 [Objective] To investigate the effect of CXCL12 / CXCR4 on the migration of oligodendrocyte precursor cells (OPCs) in rats and its regulatory mechanism. [Method] The effects of different concentrations of CXCL12 (0 ng / ml, 5 ng / ml, 10 ng / ml, 20 ng / ml) on migration of OPCs in rats were detected by Boyden chamber. The expression of MEK1 / 2 pathway. CXCR4 shRNA was used to inhibit the expression of CXCR4 protein. U0126 blocked MEK1 / 2 pathway. Western blotting was used to detect the expression of ERK and p-ERK in MEK1 / 2 pathway Changes, through the boyden chamber detection of rat OPCs migratory capacity changes. [Results] CXCL12 could significantly promote the migration of OPCs in rats. With the increase of extracellular CXCL12 concentration, the expression of CXCR4 in OPCs increased gradually. Compared with 0 ng / ml, CXCL12 concentration was 10 ng / ml and 20 ng / ml CXCR4 protein relative expression was significantly increased, the difference was significant. And significantly increased the phosphorylation level of ERK in MEK1 / 2 pathway protein. The inhibitory effect of CXCL12 on the migration of oligodendrocyte precursor cells was significantly inhibited and the phosphorylation of ERK in MEK1 / 2 pathway protein was also significantly inhibited ; After blocking the MEK1 / 2 pathway with U0126, the promoting effect of CXCL12 on the migration of rat OPCs was significantly inhibited. [Conclusion] CXCL12 / CXCR4 can regulate the migration of rat OPCs through the MEK1 / 2 pathway, providing the experimental basis for further exploration of the treatment of spinal cord injury.
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