SOD类似物阻断百草枯诱导的N27细胞凋亡的作用

Protective effect of SOD mimetic on the apoptosis of N27 cells induced by paraquat

目的探讨在离体培养的细胞中,SOD类似物[manganese(Ⅲ)meso-tetrakis(N,N′-diethylimidazolium-2-yl)porphyrin,MnTDM]阻断百草枯诱导的N27细胞凋亡的作用。方法以N27细胞为多巴胺能神经元的细胞模型,检测不同浓度的MnTDM对百草枯诱导的N27细胞凋亡的保护作用,四甲基偶氮唑盐(MTT)法检测细胞活性及代谢状态;电镜观察凋亡形态;免疫细胞化学染色法观察凋亡相关蛋白Bax、Bcl-2蛋白的表达。结果经百草枯作用后N27细胞活性下降,且其下降程度与百草枯浓度的升高呈线性关系,MnTDM明显阻断百草枯诱导的细胞活性下降(P<0.05),且该阻断作用与MnTDM的浓度成正相关;MnTDM预处理后,电镜观察到细胞凋亡形态好转,凋亡相关蛋白Bcl-2表达升高,Bax表达降低,Bcl-2/Bax值升高。结论MnTDM对百草枯介导的凋亡有一定的保护作用,提示其可能对帕金森病患者的临床防治有一定作用。

Purpose To determine if manganese （Ⅲ ） meso-tetrakis （ N, N＇-diethylimidazolium-2-yl） porphyfin （MnTDM）, a superoxide dismutase （SOD） mimetic, can prevent against paraquat（PQ）induced apopto- sis in N27 cells. Methods When cells were pretreated with MnTDM prior to PQ, the cell viability and metabolism status were measured by MTT assay. The nuclear morphological apoptosis change was evaluated by electron microscopy. To explore the protective mechanism of MnTDM in PQ-induced N27 cells, Bcl-2 and Bax protein expression were measured by immunocytoehemistry. Results MnTDM significantly inhibited the paraquat-induced decreased cell viability and dopaminergie cell density depletion in the in N27 cell line by a dose-dependent manner. MnTDM promoted Bcl-2 expression, while inhibited Bax expression induced by PQ. The rate of Bel-2/Bax was increased. Conclusion These results indicated that pretreatment of N27 cells with MnTDM could block PQ mediated cytotoxicity and apoptosis by Bel-2 and Bax expression. It is suggested that MnTDM may have the potential clinical therapeutic benefits for PD.