雌激素对6-羟基多巴胺损伤黑质多巴胺能神经元的保护作用  

Estrogen protects the dopaminergic neurons in substantia nigra against damage induced by 6-hydroxydopamine

作　　者：孟金兰[1] 马元怡[1] 罗海芸[1] 孔淑贞[1] 何永文[1] 董宝财[1] 吴诗昊[1] 何敏[1] 

机构地区：[1]昆明医学院生理学教研室

出　　处：《生理学报》2008年第3期369-374,共6页Acta Physiologica Sinica

基　　金：the Natural Science Foundation of Yunnan Province (No. 2001C0005R)

摘　　要：本研究以P50听觉诱发电位(P50auditory evoked potential,P50)和酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞计数作为黑质功能和形态学指标,动态追踪研究雌激素对6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损伤黑质多巴胺(dopamine,DA)能神经元的作用。将大鼠分为4组:(1)正常雌性大鼠对照组;(2)单纯帕金森氏病(Parkinson's disease,PD)模型组;(3)双侧去卵巢PD模型组;(4)去卵巢回补3d雌激素的PD模型组。在大鼠清醒和安静的生理状态下连续14d记录黑质的P50,并检测黑质TH+细胞数目的变化。结果显示:单纯PD模型大鼠黑质P50的T/C值较正常雌鼠降低40.60%(P<0.01),其损伤侧黑质TH+细胞数目减少64.74%(P<0.01);去卵巢PD模型大鼠黑质P50的T/C值较单纯PD模型大鼠进一步降低45.88%(P<0.01),同时其黑质TH+细胞数目值也进一步减少57.26%(P<0.01),表明急性缺乏生理水平性腺雌激素将增大6-OHDA损伤黑质DA能神经元的程度,同时使黑质的感觉门控(sensory gating,SG)功能明显受损;去卵巢后回补3d生理剂量雌激素,可明显改善大鼠黑质的SG功能,提高TH+细胞数量(与去卵巢PD模型大鼠比较,P<0.01),其黑质损伤程度与单纯PD模型大鼠相当。以上结果提示,生理水平的雌激素具有提高黑质DA能神经元对伤害性刺激耐受性的神经保护作用。缺乏性腺源性的雌激素时,及时给予生理剂量的雌激素可以减轻神经毒素6-OHDA对黑质DA能神经元结构和功能的损伤。Substantial evidence strongly implies that sensory gating P50 （also called P50 auditory evoked potential, P50） and dopaminergic neurotransmitters are related. In animal experiment, P50 can be recorded in an awake and quiet state with freedom of movement. Until now there is lack of animal experimental data on the supportive effect of estrogen on function of dopamlnergic neurons in substantia nigra （SN） in physiological state. In the present study, female Sprague-Dawley （SD） rats were used as subjects. The animals were divided randomly into four groups： （1） control group （normal animals）; （2） Parkinson＇s disease （PD） model group： the fight SN was lesioned with 6-hydroxydopamine （6-OHDA）; （3） PD model with bilateral ovariectomized group （OVX-PD）： bilateral ovariectomy was performed before administration with 6-OHDA; （4） estrogen ＋ PD model with bilateral ovariectomized group （OVX-E2-PD）： physiological dose of estrogen was given to the bilateral ovariectomy animals before admi- nistration with 6-OHDA. P50 induced by two brief acoustic stimuli were recorded in the right SN and the number of TH^＋ dopaminergic neurons in the SN stained by immunohistochemistry was calculated after the determination of PS0. The results showed that in the PD model group, the testing/conditioning （T/C） ratio of PS0 decreased by 40.60% and the number of TH^＋ cells in the right SN decreased by 64.74% as compared with that in the control group （P〈0.01）; In the OVX-PD group, the T/C ratio of P50 decreased by 45.88% and the number of TH^＋ cells was reduced by 57.26% as compared with that in the PD group （P〈0.01）. Administration with 6-OHDA into the SN pars compacta of ovariectomized rats caused more decrease in the number of TH^＋ cells as well as more damage to the function of sensory gating in SN. While in OVX-E2-PD group, intramuscular injection with estrogen at physiological dose 3 d before 6-OHDA administration decreased the degree of damage to the SN functio

关 键 词：感觉门控 P50听觉诱发电位 雌激素 黑质 多巴胺能神经元 6-羟基多巴胺 

分 类 号：R742.5[医药卫生—神经病学与精神病学]