Calbindin D28k对帕金森病模型小鼠纹状体凋亡相关蛋白表达的影响

目的观察1-甲基4-苯基1,2,3,6四氢吡啶(MPTP)致帕金森病(PD)模型小鼠黑质多巴胺能神经细胞过表达Calbindin D28k(CB)时,纹状体细胞抗损伤作用机制。方法选择C57BL/6小鼠连续5 d腹腔注射MPTP,构建成功PD模型小鼠30只,随机分为模型组,人类免疫缺陷病毒(HIV)Ⅰ组(注射HIV Ⅰ)和CB-HIV-Ⅰ组(注射CB-HIV-Ⅰ),每组10只,连续6周对各组小鼠行为学检测,Western blot法检测各组小鼠CB,Bcl 2和Bax的表达变化。结果与模型组和HIV-Ⅰ组比较,CB-HIV-Ⅰ组小鼠各时间点移动格子次数,第1、2、5和6周站立次数,第6周时游泳和悬挂时间,差异有统计学意义(P0.05,P0.01);CB-HIV Ⅰ组小鼠中脑黑质中CB的表达量显著升高(P0.05),纹状体细胞中Bcl-2的表达量亦明显升高(P0.01),而Bax的表达量明显降低(P0.01)。模型组和HIV-Ⅰ组上述指标差异无统计学意义(P0.05)。结论黑质多巴胺能神经细胞过表达CB时,纹状体细胞Bcl-2/Bax表达上调,提示其与纹状体细胞抗凋亡能力增强有关。

Effects of calbindin D28k on expression of apoptosis-associated proteins in the striatum of the mouse model of Parkinson's disease

Objective To study the effect of over-expression of calbindin D28k(CB) in substantia nigra dopaminergic neurons on the expression of Bcl-2 and Bax in the striatum of l-methyl-4-phenyl -1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson's disease(PD) and to discover CB's neuroprotective mechanism at protein expression levels.Methods C57BL/6 mice were injected intraperitoneally with MPTP for 5 days to establish 30 mouse models of PD.Then, the mice were randomly divided into 3 groups (10 mice/group):control group,HIV-Ⅰ group (injected with HIV-Ⅰ),and CB-HIV-Ⅰ group (injected with CB-HIV-Ⅰ).The Western blot was used to detect the expression levels of CB,Bcl-2 and Bax.Results Compared with control group and HIV- Ⅰ group,the expression of CB and bcl-2 increased (P < 0.05,P < 0.01).while the expression of bax decreased (P < 0.01) in CB-HIV- Ⅰ group.Conclusion The over-expression of CB in substantia nigra's dopaminergic neurons may promote striatum cells' resistance to apoptosis, which is related to the increase in Bcl-2/Bax ratio.