p38MAPK抑制剂对MPTP模型小鼠黑质多巴胺能神经元的保护作用

被引:6
作者
魏子峰 [1 ]
刘江 [1 ]
周洪霞 [1 ]
张田 [2 ]
张作凤 [1 ]
李冉 [3 ]
张宇新 [1 ]
机构
[1] 河北联合大学基础医学院解剖学教研室
[2] 河北联合大学生理学教研室
[3] 河北联合大学组织胚胎学教研室
关键词
帕金森病; p38蛋白激酶; 酪氨酸羟化酶; 1-甲基-4-苯基-1,2,3,6四氢吡啶; 小鼠;
D O I
暂无
中图分类号
R742.5 [震颤麻痹综合征];
学科分类号
100204 [神经病学];
摘要
目的:研究SB239063在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中抑制p38丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)活化对多巴胺(DA)能神经元的保护作用。方法:雄性C57BL/6N小鼠随机分为MPTP(30 mg/kg)模型组;SB239063(5 mg/kg)抑制剂组;SB239063(15 mg/kg)抑制剂组;SB239063(25 mg/kg)抑制剂组。抑制剂组于每次注射MPTP前3 h腹腔注射SB239063;对照组注射与模型组和抑制剂组等量生理盐水和DMSO。采用免疫组织化学和免疫蛋白印迹法观察各组小鼠黑质酪氨酸羟化酶(TH)和磷酸化p38蛋白激酶(p-p38 protein kinase,p-p38MAPK)之间表达变化的关系。结果:模型组小鼠黒质区p38MAPK显著活化,同时伴有TH阳性神经元明显丢失;SB239063 15 mg/kg与25 mg/kg组均可明显减少TH神经元丢失,而5 mg/kg组无显著影响;免疫荧光双标记结果显示p38MAPK与TH阳性神经元存在共表达。结论:p38MAPK对PD模型小鼠中脑黑质多巴胺能神经元丢失可能有重要调控作用,SB239063对多巴胺神经元具有一定的神经保护作用。
引用
收藏
页码:330 / 334
页数:5
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