骨髓间充质干细胞调节大鼠视神经损伤后小胶质细胞的活化

背景:外伤性视神经损伤是引起视力丧失的重要原因,治疗方法也比较局限,为探求更好的治疗方法,该实验从小胶质细胞方向入手进行探究。在神经病理条件下,激活小胶质细胞能够维持中枢神经系统的稳定,但小胶质细胞过度活化会产生大量的炎症因子,使损伤进行性加重。目的:探讨视神经损伤后小胶质细胞活化情况以及骨髓间充质干细胞对其过度表达的调节作用。方法:选取8周龄SD大鼠18只,将其随机分为移植组、模型组和假手术组,每组6只,其中模型组、移植组选取左眼进行视神经钳夹造模后分离视网膜和视神经,假手术组只分离视网膜和视神经,不进行钳夹,移植组在损伤后立即向左眼玻璃体内注入第3代骨髓间充质干细胞(注入细胞1×108,细胞量为2μL),模型组、假手术组玻璃体内注入等量的PBS,术后15 d全部处死,在灌流固定后取视网膜连带视神经用于苏木精-伊红染色和免疫组织化学检测。结果与结论:模型组视神经及视网膜小胶质细胞活化标记物Ox-42以及炎症因子TNF-α的表达量均高于假手术组(P<0.05),移植组视神经及视网膜中Ox-42和TNF-α表达量降低(P<0.05)并且接近假手术组水平。结果表明,小胶质细胞的过度活化与视神经损伤相关,骨髓间充质干细胞可以抑制小胶质细胞过度活化及炎症因子的释放,从而在一定程度上保护视网膜和视神经免受损伤。

Effect of bone marrow mesenchymal stem cells on microglial activation after optic nerve injury in rats

BACKGROUND:Traumatic optic nerve injury is an important cause of vision loss,and the treatment methods are relatively limited.In order to find a better treatment method,this experiment started from the direction of microglia.Under neuropathological conditions,activation of microglia can maintain the stability of the central nervous system,but excessive activation of microglia can produce a large number of inflammatory factors that progressively aggravate the damage.OBJECTIVE:To investigate the activation of microglia after optic nerve injury and the effect of bone marrow mesenchymal stem cells(BMSCs)on the overexpression of microglia.METHODS:There were 18 Sprague-Dawley rats,8 weeks of age,which were divided into BMSCs transplantation group,model group and sham operation group,with 6 rats in each group.In the model group and BMSCs transplantation group,the rat’s left eye was selected to separate the retina and optic nerve after the optic clamping of the optic nerve.The sham operation group only separated the retina and optic nerve with no clamping.In the BMSCs transplantation group,the left eye vitreous body was injected with quantitative passage 3 BMSCs(1×10^8 cells,2μL)immediately after the injury.While in the model group and sham operation group,the same amount of PBS was injected into the vitreous body.All the rats were sacrificed at 15 days postoperatively.After perfusion and fixation,the retina with optic nerve was taken for hematoxylin-eosin staining and immunohistochemical detection.RESULTS AND CONCLUSION:The expression levels of Ox-42 and tumor necrosis factorαwere significantly higher in the model group than in the sham operation group(P<0.05),while the expression of Ox-42 and tumor necrosis factorαin the optic nerve and retina in the BMSCs group was decreased and almost the same to that in the sham operation group.Therefore,excessive activation of microglia is associated with optic nerve injury,and BMSCs can inhibit the excessive activation of microglia and release of inflammatory factors,thus protecting the retina and optic nerve from traumatic injury to some extent.