雌激素对雄性大鼠缺血性脑损伤的神经保护作用及其可能机制

Neuroprotective effect and its mechanism of estrogens in male Sprague-Dawley rats with cerebral ischemia

目的探讨雌激素对雄性大鼠局灶性脑缺血的神经保护作用及其可能机制。方法随机将大鼠分为雌激素预处理组、雌激素+他莫昔芬预处理组和对照组,采用线栓法制作大鼠大脑中动脉闭塞(MCAO)模型,观察缺血后2h和24h脑梗死体积、大鼠死亡率、神经功能缺损程度、神经元凋亡以及Bcl-2、Bax、p53蛋白的表达。结果缺血后2h和24h,雌激素预处理组较对照组脑梗死体积小、死亡率低、神经功能缺损程度轻、神经元凋亡少,并抑制Bax、p53表达,促进Bcl-2蛋白表达。雌激素受体拮抗剂他莫昔芬可抑制这一作用。结论雌激素对雄性大鼠缺血性脑损伤具有明显的神经保护作用。对基因和非基因因素的影响是神经保护作用的可能机制。

Objective To observe the neuroprotective role and its mechanism of estrogens in male Sprague-Dawley rats with focal cerebral ischemia. Methods The rats were randomly divided into three groups： E2-pretreat group, E2 ＋ TAM （ tamoxifen）-pretreat group and control group. The models of cerebral ischemia were maded by occlusion middle cerebral artery using an intraluminal filament method. 2 and 24 hours after focal cerebral isehemia, the neurological deficit seores and the death rate of rats were evaluated. 2,3,5-triphenyhetrazolium chloride （TTC） stain was used to assess the volume of infarction. Terminal transferase dUTP nick ending labeling （TUNEL） and immunohistochemistry were carried to observe neuron apoptosis and the expressions of Bcl-2, Bax and p53. Results Compared with control group, the volumes of infarction, death rates, neurological deficit scores and the numbers of neuron apoptosis both at 2 and 24 h were significantly decreased in E2-pretreated group （ all P 〈 0. 05 ）. Lower expression of Bax, p53 and higher expression of Bcl-2 were also found. TAM （E2 antagonist） prevented these effects of E2. Conclusions E2 ,nay play protective role on cerebral ischemia in rats. Regulation of gene expression and other factors is involved in its mechanism.