p38MAPK抑制剂对MPTP模型小鼠黑质多巴胺能神经元的保护作用  

Protective effect of p38MAPK inhibitor on dopaminergic neurons in the substania nigra of MPTP model mice

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] 

机构地区：[1]河北联合大学基础医学院解剖学教研室,唐山063000 [2]河北联合大学生理学教研室,唐山063000 [3]河北联合大学组织胚胎学教研室,唐山063000

出　　处：《神经解剖学杂志》2014年第3期330-334,共5页Chinese Journal of Neuroanatomy

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。Objective To investegate the protective effect of SB239063 on dopaminergic neurons in the substania nigra（SN） of MPTP-induced mouse model of Parkinson Disease （PD） through inhibition of p38 mitogen-activated protein ki-nase （p38MAPK） activation. Methords： Male C57BL/6N mice were randomly divided into MPTP model group （30 mg/kg） ; SB239063 inhibitor group （ 5 mg/kg）, SB239063 inhibitor group （ 15 mg/kg） and SB239063 inhibitor group （ 25mg/kg）. The inhibitor group mice were treated with SB239063 （intraperitoneal injection） 3 hours before injection ofMPTP; Control mice were administrated with saline and DMSO as much as the model group received. Immunohistochem-istry and Western Blot were used to observe the relationship between TH and p38MAPK expression change in the SN ofmidbrain. Results： Phosphorylated p38 mitogen-activated protein kinase （p-p38MAPK） was remarkably detected in theSN, along with the decreased numbers of tylosine hydroxylase （ TH ） -positive neurons ; By contrast, the loss of TH wasalleviated by SB239063 （15 mg/kg and 25 mg/kg, respectively）, and SB239063 （5 mg/kg） has no significant effect onthe mentioned above changes, p38MAPK positive cells were colocalized with TH by double immunofluoreseenee labeling.Conclusion： In the mouse model of Parkinson＇s Disease, p38MAPK may regulate the lossing of dopaminergic neurons inthe SN of midbrain, SB239063 might have neuroprotective effect on dopaminergic neurons.

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 

分 类 号：R742.5[医药卫生—神经病学与精神病学]