人参皂苷Rg1对多巴胺能神经元的保护作用及ICI182,780的阻断作用

目的研究人参皂苷Rg1对去卵巢（ovariectomized,OVX）帕金森病（Parkinson disease,PD）模型大鼠黑质（substantianigra,SN）酪氨酸羟化酶（tyrosine hydroxylase,TH）表达的影响以及ICI182,780的阻断作用。方法雌性Wistar大鼠随机分为正常组、OVX组、6-hydroxydopamine（6-OHDA）组、Rg1＋6-OHDA组及ICI＋Rg1＋6-OHDA组。大鼠OVX后应用6-OHDA单侧损毁内侧前脑束（medial forebrain bundle,MFB）制备PD模型,腹腔注射Rg1或侧脑室同时给予雌激素受体（estro-gen receptor,ER）拮抗剂ICI182,780,免疫组织化学技术检测TH阳性神经元,RT-PCR技术检测SN内TH基因的表达。结果OVX大鼠SN内TH基因的表达较正常大鼠明显降低（P〈0.05）。6-OHDA制备的PD模型组损毁侧SN内TH阳性神经元数量及TH基因表达较健侧明显降低（P〈0.01）。与模型组相比,Rg1可显著提高损毁侧大鼠SN内TH阳性神经元数量及TH基因的表达（P〈0.01）。此效应可以被ER拮抗剂ICI182,780完全阻断（P〈0.01）。结论ER拮抗剂ICI182,780可以阻断人参皂苷Rg1对OVX PD模型大鼠黑质多巴胺能神经元的保护作用。

Neuroprotective effect of ginsenoside Rg1 on dopaminergic neurons and blocking effect of ICI182,780

Objective To investigate the neuroprotective effect of ginsenoside Rg1 on the tyrosine hydroxylase(TH)expression in the rat model of Parkinson disease(PD)and the blocking effect of ICI182,780 on the neuroprotection.Methods Female Wistar rats were randomly divided into five groups:control group,ovariectomized(OVX)group,6-hydroxydopamine(6-OHDA)group,Rg1 6-OHDA group and ICI Rg1 6-OHDA group.The 6-OHDA was injected into the medial forebrain bundle(MFB)to induce OVX PD rat model,and then the PD rats were treated with vehicle,ginsenoside Rg1 in the absence or presence of estrogen receptor(ER)antagonist ICI182,780.The changes of tyrosine hydroxylase(TH)immunoreactive neurons and TH gene expression were detected using immuohistochemistry and RT-PCR technology.Results Compared with the normal rats,TH gene expression in SN significantly decreased in the OVX group(P<0.05).TH immunoreactive neurons and TH gene expression in the injured side in 6-OHDA group significantly decreased compared with the uninjured side.Rg1 could prevent the 6-OHDA-induced decrease of TH immunoreactive neurons and TH gene expression in the ipsilateral SN compared with 6-OHDA group(P<0.01).The neuroprotective effects could be completely blocked by ER antagonist ICI182,780(P<0.01).Conclusion ER antagonist ICI182,780 could block the neuroprotective effect of ginsenoside Rg1 on the dopaminergic neurons in the OVX rat model of PD.