雌激素对绝经后雌性大鼠缺血性脑损伤的保护作用及机制

Neuroprotective effect of estrogens and its mechanism in reproductively senescent female rats with cerebral Ischemia

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机制。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、血清NO及NOS浓度。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、血清NO及NOS浓度高;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、血清NO及NOS浓度高。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;雌激素提高血清NO及NOS浓度是神经保护作用的可能机制;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。

To observe the neuroprotective effect of estrogens and its mechanism in reproductively senescent female rats with cerebral 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 made by occlusion of middle cerebral artery using an intraluminal filament method. 24 hours after focal cerebral ischemia, the infarct volume, the neurological deficit scores and NO and NOS concentrations in serum were evaluated. Results Compared with control group, the infarct volumes and neurological deficit scores were significantly decreased in E2-treat group and E2 ＋ tamoxifen-treat group. Higher NO and NOS concentrations in serum were also found. Compared with E2 ＋ tamoxifen-treat group, the infarct volume and neurological deficit score were significantly decreased in g2-treat group. Higher NO and NOS concentrations in serum were also found in E2-treat group. Conclusions E2 may play a protective role on cerebral ischemia in reproductively senescent female rats. The therapeutic windows is up to 6 hours. Increase of NO and NOS concentrations in serum is involved in its mechanism. Tamoxifen, E2 antagonist, may partly prevent these effects.