雌激素对绝经后雌性大鼠缺血性脑损伤的保护作用及一氧化氮合酶表达的影响

目的观察雌激素对绝经后雌性大鼠缺血性脑损伤的保护作用及一氧化氮合酶表达的影响。方法随机将12月龄雌性大鼠分为假手术组(A组)、对照组(B组)、雌激素处理组(C组)、雌激素 他莫西芬处理组(D组),采用线栓法制作大鼠大脑中动脉闭塞(MCAO)模型,观察缺血后24h脑梗死体积、神经功能缺损程度;采用免疫组织化学法观察脑组织中神经元型NOS(nNOS)及内皮型NOS(eNOS)的表达水平。结果雌激素处理组及雌激素 他莫西芬处理组均较对照组脑梗死体积小、神经功能缺损轻,但雌激素处理组较雌激素 他莫西芬处理组脑梗死体积小、神经功能缺损轻;雌激素处理组较对照组nNOS表达降低,eNOS表达增强。结论雌激素对绝经后雌性大鼠缺血性脑损伤具有明显的保护作用,时间窗为6h;雌激素受体拮抗剂他莫西芬可部分阻断雌激素的神经保护作用;雌激素增强eNOS及降低nNOS的表达水平是神经保护作用的可能机制。

Neuroprotective effect and expression changes nitric oxide synthase of estrogens in reproductively senescent female rats with cerebral Ischemia

Objective To observe the neuroprotective effect and expression changes nitric oxide synthase of estrogens in reproductively senescent female rats with cererbal ischemia.Methods The 12-month old rats were randomly divided into four groups:sham group,control group,E2- treat group and E2- tamoxifen-treat group.The models of cerebral ischemia were maded by occlusionmiddle cerebral artery using and intraluminal filamentmethod.24 hours after focal cerebral ischemia,the infarct volume and the neurological deficit scores were evaluated.Expression changes of nNOS and eNOS were observed by immunohistochemical method.Results Compared with control group,the infarct volumes and neurological deficit scores were significantly decreased in E2- treat group and E2- tamoxifen-treat group.But Compared with E2- tamoxifen-treat group,the infarct volume and neurological deficit score were significantly decreased in E2- treat group.Compared with control group,the expression of eNOS was enhanced obviously while nNOS slightly in E2- treat group.Conclusions E2 may play protective role on cerebral ischemia in reproductively senescent female rats.The therapeutic windows is up to 6 hours.Tamoxifen,E2 antagonist,partly prevented these effect.Increase of the expression of eNOS and decrease of the expression of nNOS are involved in its mechanism.