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.pdfVIP

生理学报 Acta Physiologica Sinica, June 25, 2008, 60 (3): 369-374 369 研究论文 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 ** * 孟金兰 ，马元怡，罗海芸，孔淑贞，何永文，董宝财，吴诗昊，何敏 昆明医学院生理学教研室，昆明 650031 摘 要：本研究以P50 听觉诱发电位(P50 auditory 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3 d 雌激素的PD 模型组。在大鼠清醒和安静的生理状态下连续14 d 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% (P0.01) ，其损 伤侧黑质TH+ 细胞数目减少64.74% (P0.01)；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% (P0.01) ，同时其黑质TH+ 细胞数目值也进一步减少57.26% (P0.01) ，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3 d 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。 关键词：感觉门控；P 5 0 听觉诱发电位；雌激素；黑质；多巴胺能神经元；6 - 羟基多巴胺 中图分类号：R 3 3 8 Estrogen protects the dopaminergic neurons in substantia nigra against damage induced by 6-hydroxydopamine MENG Jin-Lan**, MA Yuan-Yi, LUO Hai-Yun, KONG Shu-Zhen, HE Yong-Wen, DONG Bao-Cai, WU Shi-Hao, HE Min* Department of Physiology, Kunming Medical University, Kunming 650031, China Absract: 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 dopaminergic neurons in substantia nigra (SN) in physiological state. In the present study, female Sprague-Dawley (SD) rats were used as subjects. The animals were d