罗格列酮联合替米沙坦在治疗小鼠MPTP致帕金森病中的神经保护作用  

Neuroprotective effects of rosiglitazone combined with telmisartan in treatment of the MPTP-induced Parkinson's disease of mouse model

作　　者：张乘云[1] 张宇新[1] 司道文[1] 刘江[1] 王茜[1] 张作凤[1] 

机构地区：[1]河北联合大学基础医学院人体解剖学系,唐山063000

出　　处：《神经解剖学杂志》2015年第5期623-628,共6页Chinese Journal of Neuroanatomy

基　　金：河北省科技厅自然科学基金资助课题(C2004000689);河北省科技厅博士基金资助课题(05547008D-4);河北省科技厅科学技术与社会发展计划项目资助课题(04276135)

摘　　要：目的:探讨罗格列酮与替米沙坦单独用药与联合用药对帕金森病(PD)多巴胺(DA)能神经元的保护作用。方法:采用MPTP制备PD亚急性小鼠模型,免疫组织化学和免疫蛋白印迹法检测小鼠中脑黑质酪氨酸羟化酶(TH)、诱导型一氧化氮合酶(i NOS)、NADPH氧化酶活化蛋白(p47)的表达变化,观察单独给予罗格列酮、替米沙坦及两者联合给药后对上述变化的影响。结果:与对照组相比,模型组小鼠出现震颤、步态迟缓等PD样症状,黑质区TH阳性神经元缺失,i NOS、p47阳性细胞明显增多,两蛋白水平亦升高;单独给予罗格列酮或替米沙坦后,上述情况得到改善;罗格列酮和替米沙坦联合用药后,改善程度较单独用药更为明显。结论:罗格列酮联合替米沙坦通过抑制PD小鼠模型中脑黑质i NOS和p47的表达,对DA能神经元起到一定的保护作用。Objective： To investigate the neuroprotective effects of rosiglitazone and telmisartan administered alone and in combination on the dopaminergic neurons （DA） in a mouse model of Parkinson＇s disease （PD）. Methods ：The suba- cute PD mouse model was induced by MPTP. Both immunohistochemistry and Western blot were used to detect the ex- pression changes of tyrosine hydroxylase （ TH）, inducible nitric oxide synthase （iNOS） and NADPH oxidase protein （ P47 ） in the substantia nigra of midbrain. After rosiglitazone and telmisartan administered alone and in combination, the above changes were also studied, respectively. Results： Compared with the control group, the animals in MPTP model group showed the typical symptoms of PD with tremor and slow gait, the marked loss of TH positive neurons, the signifi- cantly increased number of iNOS and p47 positive cells and the higher expression levels of iNOS and p47. The above phe- notypes of PD could be improved by the single treatment with rosiglitazone telmisartan, and the improvement was more ob- viously by the combination treatment. Conclusion：In the mouse model of PD, the dopaminergic neuroprotection ism of rosiglitazone and telmisartan in combination might be mediated by inhibiting the expressions of iNOS and p47 in the sub- stantia nigra of midbrain.

关 键 词：帕金森病 酪氨酸羟化酶 诱导型一氧化氮合酶 NADPH氧化酶 罗格列酮 替米沙坦 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]