人参皂苷Rg1和IGF-Ⅰ对帕金森病小鼠DA能神经元作用

目的观察人参皂苷Rg1、胰岛素样生长因子Ⅰ（IGF-Ⅰ）及二者合用对小鼠黑质纹状体系统多巴胺（DA）能神经元的神经保护作用。方法 C57BL/6去卵巢（OVX）小鼠50只,采用腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）方法制备帕金森病（PD）模型小鼠,随机分为对照组、MPTP组、Rg1组（10mg/kg腹腔注射）、IGF-Ⅰ组（0.5g/L侧脑室注射）、Rg1＋IGF-Ⅰ组,每组10只。应用高效液相色谱法检测各组纹状体内DA的含量,免疫组织化学染色法检测黑质内酪氨酸羟化酶免疫阳性（TH-IR）神经元数目。结果 MPTP组纹状体内DA含量、黑质TH-IR神经元数目较对照组明显降低,差异有显著性（F=21.23、45.45,q=11.67、14.24,P〈0.01）。Rg1组、IGF-Ⅰ组及Rg1＋IGF-Ⅰ组纹状体DA含量、黑质TH-IR神经元数目较MPTP组明显升高,差异有显著性（q=5.66～17.91,P〈0.01）;Rg1＋IGF-Ⅰ组与Rg1组、IGF-Ⅰ组比较,差异有显著性（q=4.37～8.74,P〈0.05）。结论 Rg1、IGF-Ⅰ及二者合用均能够对抗MPTP对黑质纹状体系统DA能神经元的毒性作用,且Rg1与IGF-Ⅰ合用具有协同作用。

EFFECTS OF GESENOSIDE RG1 AND INSULIN-LIKE GROWTH FACTOR-ⅠON DOPAMINERGIC NEURONS IN PARKINSON＇S DISEASE MICE

Objective To investigate the neuprotective effects of ginsenoside（Rg1）,insulin-like growth factor-Ⅰ（IGF-Ⅰ）and combined treatment on nigrostriatal dopaminergic（DA）neurons in mice. Methods Fifty ovariectomized and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced Parkinson＇s disease（PD）model C57BL/6mice were evenly randomized to control group,MPTP group,Rg1group（10mg/kg,ip）,IGF-Ⅰgroup（0.5μg/μL,icv）,Rg1and IGF-Ⅰcombined group.High performance liquid chromatography-electrical chemical detection（HPLC-ECD）was used to detect the contents of DA in the striatum.The tyrosine hydroxylase-immunoreactive（TH-IR）neurons in the substantial nigra were determined by immunohistochemistry. Results The contents of DA in MPTP striatum and the numbers of TH-IR neurons in the substantial nigra significantly decreased as compared with the control group（F=21.23,45.45;q=11.67,14.24;P〈0.01）.DA content and the numbers of TH-IR neurons in the substantial nigra in Rg1,IGF-Ⅰ,and combined Rg1plus IGF-Ⅰgroups were significantly higher than that in the MPTP group（q=5.66-17.91,P〈0.01）,and the differences of that between the combination group and both Rg1and IGF-Ⅰgroups were significant（q=4.37-8.74,P〈0.05）. Conclusion Rg1or IGF-Ⅰor combined both Rg1and IGF-Ⅰcan all play a role against MPTP–induced neurotoxicity on nigrostriatal dopaminergic neurons.The combination of Rg1plus IGF-Ⅰ has a synergistic effect.