人参皂甙Rg1对帕金森病小鼠黑质JNK细胞凋亡通路的影响

THE INFLUENCE OF GINSENOSIDE Rg1 ON JNK SIGNALINGCASCADE IN PD MOUSE SUBSTANTIA NIGRA NEURONS

目的 探讨人参皂甙Rg1(ginsenosideRg1)抗帕金森病 (PD)小鼠黑质神经元凋亡的可能机制。 方法采用MPTP制备帕金森病 (PD)小鼠模型 ,经人参皂甙Rg1预处理后 ,用尼氏染色、TH和活化型caspase 3组织化学染色及TUNEL染色法观察黑质神经元的损害情况 ,并计算神经元的凋亡率 ,同时应用蛋白免疫印迹法检测黑质神经元磷酸化JNK(c Jun氨基末端激酶 )及磷酸化c Jun蛋白表达水平。 结果 人参皂甙Rg1预处理可减轻PD小鼠黑质致密带Nissl阳性神经元和TH阳性神经元的丢失现象 ,同时减少磷酸化JNK及磷酸化c Jun蛋白表达水平 ,活化型caspase 3表达减少 ,降低黑质神经元的凋亡率。 结论 人参皂甙Rg1能减少MPTP诱导的小鼠黑质神经元凋亡 ,其机制与阻断JNK细胞凋亡通路激活有关。

Objective To explore the possible molecular mechanism of Ginsenoside Rg1 preventing against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced substantia nigra neurons apoptosis in Parkinson disease(PD) mouse model. Methods C57BL mice were administrated(sc) with MPTP to produce PD mouse model.Different doses of Rg1(5.0,10.0,20.0*!mg/kg) were given(ip) prior 3*!d to MPTP in the pretreatment groups.Nissl staining,tyrosinehydroxythase(TH) immunostatining,cleaved caspase-3 immunostatining and TUNEL staining were used to observe the changes of nigra neurons,meanwhile,Western blot was used to detect the phosphorylated protein of JNK and c-Jun in substantia nigra. Results Pretreatment with Rg1 could prevent the loss of Nissl staining neurons and TH-positive neurons,inhibit JNK and c-Jun phosphorylation in SN,decrease the percent of cleaved caspase-3 and TUNEL-positive cell.Conclusion Rg1 can attenuate MPTP-induced apoptosis in substantia nigra neurons through blocking JNK signaling cascade.