泊马度胺改善脑缺血小鼠神经功能的机制研究

Study on the mechanism of the improvement of neurological function in mice with cerebral ischemia by pomalidomide

目的探讨泊马度胺(pomalidomide,Pom)对大脑中动脉闭塞模型(middle cerebral artery occlusion,MCAO)小鼠的神经保护作用及相关机制。方法雄性C57/BL6小鼠采用线栓法制成MCAO模型,成功模型随机分为假手术组(Sham组)、MCAO组、溶剂组(Vehicle组)和泊马度胺组(Pom组)。采用改良的神经功能缺损评分(mNSS)评估小鼠神经功能缺损程度,免疫荧光染色测定脑梗死灶周围增生的小胶质细胞,Western blotting检测炎症因子、神经营养因子的表达。结果同Vehicle组小鼠相对比,Pom组小鼠神经功能明显改善,小胶质细胞活化的数量明显减少,且炎症因子的表达显著降低,而神经营养因子表达增高,差异具有统计学的意义(P<0.05)。结论泊马度胺可通过抑制脑梗死后小鼠的小胶质细胞的增生,减少炎症因子的表达,还可以产生神经营养作用,有效改善脑缺血小鼠的神经功能从而产生神经保护作用。

Objective To investigate the neuroprotective effect of pomalidomide(Pom)on middle cere bral artery occlusion(MCAO)mice and its related mechanism.Methods Male C57BL6 mice were prepared into a MCAO model by suture method.After successfully establishing the models which were randomized into sham operation group(Sham group),MCAO group,solvent group(Vehicle group)and Pom group.The neurological deficits of mice were assessed by the neurological function score(mNSS).The immunofluorescence staining detected the proliferation of microglia around the infarct area.The expressions of inflammatory factors and nerve growth factors were detected by Western blotting.Results Comparing with the Vehicle group,the neurological function score of Pom group was significantly improved,the number of activated microglia was significantly reduced,and inflammatory factors were significantly decreased,and neurotrophic factors were increased.Conclusion Pomadamide can inhibit the proliferation of microglia in mice after cerebral infarction,reduce the expression of inflamma tory factors,and also produce neurotrophic effect,which can effectively improve the neurological function of cere bral ischemia and produce neuroprotective effect in mice.