去卵巢大鼠脑缺血后雌激素干预的脑保护作用及其机制的研究

The Study on Neuroprotective Effects and Mechanism of Estradiol When Administered after Cerebral Ischemic in-sult

目的:探讨雌激素能否对已经发生脑缺血的去卵巢大鼠发挥脑保护作用及可能机制是否与抗细胞凋亡有关。方法:SD雌性大鼠于去卵巢术后3周分为三组:治疗组(N=50):MCAO术后0h、3h、6h、12h、24h分为5小组(每个时间点n=10),在每个时间点给予17β-E21 mg/kg·d腹腔注射;对照组:(N=10)MCAO术后每天腹腔注射等量溶剂;假手术组(N=6):假MCAO手术后每天腹腔注射等量溶剂。术后进行神经功能缺损评分;TTC染色测量脑梗死体积;RT-PCR法测定脑组织Bcl-2mRNA,BaxmRNA的表达。结果:1.0 h、3 h、6 h、12 h治疗组的神经功能缺损评分、脑梗死体积均较对照组低(P<0.01),并且随雌激素给药时间的提前而逐渐降低。24 h治疗组与对照组比较无显著性差异(P>0.05)。2.0 h、3 h、6 h、12 h治疗组Bcl-2mRNA的表达高于对照组,BaxmRNA的表达低于对照组(P<0.01);结论:去卵巢大鼠发生脑缺血后给予雌激素治疗,雌激素仍然能够发挥脑保护作用;保护作用机制可能与通过上调Bcl-2mRNA的表达、下调Bax mRNA的表达而产生的抗细胞凋亡有关。

Objective： This study was designed to determine whether E2 treatment after ischemia exerts the neuroprotective effects and whether the effects are related to anti-apoptosis. Methods： All Female Spra-gne-Dawley rats are teamed into three groups after being ovariectomized three weeks ago. In Group 1 （ERT group）, Ovariectomized Sprague-Dawley rats were subjected to middle cerebral artery occlusion （MCAO）. And E2 was administered （100 μg/kg·d peritoneal injection ） at 0 （n=10）, 3 （n=10）, 6 （n=10）, 12 （n=10）, or 24 （n=10） hours after MCAO. In Group 2 （control group）, Ovariectomized rats（n=10） were subjected to MCAO and received vehicle instead of E2. In Group 3 （sham group）, Ovariectomized rats （OVX; n=10） were subjected to sham opera-tion and received vehicle instead of E2, and ischemic infarct volume was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression of Bcl-2mRNA and BaxmRNA in the brain were measured by RT-PCR. Results： 1. The infarct volume and neurologic impairment score of ERT rats when E2 was administered at 0,3,6,12 hours after MCAO were decreased much more than that of control rat （P〈0.01）. 2. The Bcl-2 mRNA level of ERT rats when E2 was administered at 0, 3, 6, 12 hours after MCAO was higher than that of control rat（P〈0.01）. Conclusions： E2 exerts neuroprotective effects when administered after ischemia, with a therapeutic window in a focal cerebral ischemia model of at least 12 hours. This effect of estradiol was associated with anti-apoptosis.