【摘要】 目的研究1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致帕金森病(Parkinson’s disease,PD)小鼠模型黑质内P38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路对诱导型一氧化氮合酶(inducible nitric oxide,i NOS)的表达调控作用,以探讨PD中脑黑质多巴胺能神经元变性丢失的可能机制。方法采用神经毒素MPTP制备PD小鼠模型,免疫组织化学法观察各组小鼠黑质酪氨酸羟化酶(TH)、磷酸化P38(p-P38)和诱导型一氧化氮合酶(i NOS)阳性神经元数量的改变。结果与对照组相比,模型组小鼠黑质致密带TH阳性神经元显著减少约60%(P<0.01),黑质区p-P38、i NOS阳性细胞均显著增高(P<0.01);与模型组比较,P38MAPK特异性抑制剂SB203580处理组黑质致密带TH阳性神经元细胞丢失明显减轻(28%vs.60%)(P<0.01);黑质区p-P38、i NOS阳性细胞均显著减少(P<0.01)。结论i NOS表达可能在中脑黑质DA能神经元变性丢失过程中起重要作用;P38信号通路可对中脑黑质细胞i NOS表达有重要的调控作用;P38通路抑制剂对MPTP所致帕金森病小鼠具有一定的神经保护作用。更多还原

【Abstract】 Objective To investigate the effect of P38 mitogen-activated protein kinase(P38MAPK) signaling pathway on the expression of inducible nitric oxide synthase(iNOS) in substantia nigra(SN) of the mouse models of Parkinson’s disease(PD) induced by 1-Methyl-4-phenyl-1,2,3,6-Tetrah-ydropyridine(MPTP) and further explore the possible mechanism of the dopaminergic(DA) neuron loss in SN of midbrain in PD.Methods Chronic PD model was produced by MPTP,and the expressional change of tyrosine hydroxylase(TH),p-P38 and inducible nitric oxide synthase(iNOS) in SN of midbrain were studied with immunohistochemistry.Results Compared with those control mice,the number of TH-positive neurons in SNc of midbrain in model group was distinctly reduced by about 60%(P<0.01),the number of p-P38,iNOS immunoreactive cells was specially expressed in SN area in the mice(P<0.01),In P38 inhibitor group,the number of TH-positive neurons in SN was only decreased by about 28% as compared with the control mice(60%)(P<0.01);the number of p-P38,iNOS immunoreactive cells was distinctly reduced in SN area(P<0.01).Conclusion iNOS mediates inflammatory process is detrimental to DA neurons;P38 MAPK signaling pathway may play an important role in mediating iNOS expression in SN in the MPTP model of subacute PD;SB203580 may be neuroprotective to DA neurons in SNc of midbrain in the MPTP mouse model of PD.更多还原