《中国康复理论与实践》

《中国康复理论与实践》 ›› 2009, Vol. 15 ›› Issue (02): 106-108.

• 专题 • 上一篇    下一篇

磷酸化p38MAPK在实验性自身免疫性脑脊髓炎轴索损伤中的作用

张金涛1;金香兰2;倪建强2;蒋建华2;尚晓玲2;邢广羽2;尹岭2   

  1. 1. 解放军第八十八医院神经内科，山东泰安市 271000;2. 解放军总医院神经信息中心，北京市 100853
  • 收稿日期:2008-08-19 出版日期:2009-02-01 发布日期:2009-02-01

Effect of Hyperphosphorylated p38MAPK in Experimental Autoimmune Encephalomyelitis Axonal Damage

ZHANG Jin-tao, JIN Xiang-lan, NI Jian-qiang, et al   

  1. The Department of Neurology, the 88th Hospital of PLA, Taian 271000, Shandong, China
  • Received:2008-08-19 Published:2009-02-01 Online:2009-02-01

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摘要： 目的 观察p38MAPK在实验性自身免疫性脑脊髓炎(EAE )中的活化及其与早期神经元轴索损伤的关系和变化规律，以及p38MAPK阻滞剂SB203580对轴索损伤的调节作用。方法 使用SJL雌性小鼠建立EAE模型，分别对模型组、SB203580组和对照组各时间点取脑和脊髓，行HE和Luxol Fast Blue（LFB）染色，并行磷酸化p38MAPK抗体染色；对相邻脑组织切片同时行淀粉样前体蛋白（APP）免疫组化检测。用图像分析系统对脑白质病灶内神经元胞浆阳性信号数目、覆盖面积及阳性信号平均密度值进行测量。结果 PLP肽段免疫的小鼠发病具有缓解-复发的特点，局部白质区域出现脱髓鞘改变。与模型组比较，SB203580组改变较轻，符合其行为学观测结果，且小鼠的体重增加明显高于模型组（P<0.01）。除对照组，其余各组在各时间点均有APP蛋白表达。与模型组相比，SB203580组干预后APP蛋白表达较轻，阳性细胞数目与强度均明显下降（P<0.01）；磷酸化p38MAPK在EAE小鼠免疫后第7天就有明显表达。与模型组相比，SB203580组p38MAPK表达较轻，阳性数目与强度均明显下降（P<0.01）。结论 p38MAPK阻滞剂SB203580不仅能够抑制EAE中p38MAPK活化，而且可以有效下调EAE轴索损伤的标志性指标APP的表达；p38MAPK可能参与了EAE的轴索损伤过程。

关键词: 实验性自身免疫性脑脊髓炎, SJL小鼠, 磷酸化p38MAPK, 淀粉样前体蛋白, 轴索损伤

Abstract: Objective To explore the mechanism about the expression of the hyperphosphorylated p38MAPK in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) mouse and its relationship to the axonal damage, and investigate the potential regulation of SB203580 to the damaged axons in the CNS of EAE mouse.Methods SJL/J mice were used to establish the EAE model. Brain and spinal cord of EAE mice in the model group, SB203580 group and control group were used respectively at different time points. Stained with HE and Luxol Fast Blue (LFB), also the immunohistochemical detection was conducted with parallel phosphorylation of p38MAPK antibody staining and APP staining at the same time. By image analysis system, the number of positive signals, the coverage and the average density value in the cytoplasm of neuron in white matter lesions were measured.Results The model of EAE mice induced by PLP peptide manifested significant neurological symptoms, signs and features of relapse and remitting. Demyelinating change was observed in local regional white matter region. Compared with the model group, SB203580 group changed lighter, with its behavioral observations and had a significant weight gain (P<0.01). In addition to the control group, amyloid precursor protein (APP) expression was detected in other groups at various time points. Compared to the model group, APP expression was slighter than in SB203580 group. The number of positive cells and strength was significantly lower in the SB203580 group (P<0.01); expression of p38MAPK in EAE mice was observed at the earlier 7th day after immunization. Compared to the model group, expression of SB203580 group was lighter, positive number and intensity decreased markedly (P<0.01).Conclusion p38MAPK blockers SB203580 can not only inhibit activation of the p38MAPK in EAE mice, but also effectively reduce expression of APP which is symbolic target of EAE axonal injury, it is confirmed that the p38MAPK is indeed involved in the EAE axonal injury.

Key words: experimental autoimmune encephalomyelitis, SJL/J mice, hyperphosphorylated p38MAPK, myloid precursor protein, axonal damage