雌激素对脑卒中后抑郁大鼠行为学和神经再生的剂量相关性研究

目的探讨雌激素对脑卒中后抑郁(PSD)大鼠行为学和神经元再生的剂量相关性。方法双侧卵巢切除的SD雌性大鼠,应用大脑中动脉栓塞和慢性不可预见温和刺激的方法建立大鼠PSD模型。将大鼠分为对照组和雌激素不同干预剂量(0μg、1μg、10μg、25μg、100μg)组。雌激素持续干预2周后,观察大鼠行为学改变和侧脑室室下区(SVZ)神经元再生的变化。结果雌激素干预2周后,与雌激素0μg组比较,10μg组和25μg组大鼠的行为学数据有明显改善(P0.05)。免疫组化结果显示,与雌激素0μg组比较,10μg组和25μg组SVZ区神经元数增加明显(分别为P0.01,P0.05)。结论适度生理剂量雌激素可通过增加SVZ神经元改善PSD大鼠的抑郁状态。

Effects of Different Doses of Estrogen on Behaviors and Neurogenesis of Post-stroke Depression Rats

KEY WORDS estrogen; post-stroke depression; subventricular zone; behavior; neurogenesis ABSTRACT Aim To research the effects of different doses of estrogen on behaviors and nearogenesis of post- stroke depression （PSD） rats. Methods The PSD animal model was built by middle cerebral artery occlusion （MCAO） and chronic mild stress （CMS） after ovariectomy surgery （OVX）. The rats were divided into six groups： a control group （aiter OVX group）, estrogen 0 μg group （0 μg group）, estrogen 1 μg group （1 μg group）, estrogen 10 μg group （10 μg group）, estrogen 25 μg group （25 μg group） and estrogen 100 μg group （100 μg group）. The estrogen groups were the groups in which PSD rats were injected subcutaneously with different doses of estradiol for two weeks. The changes of the behaviors and neurogenesis in subventficular zone （SVZ） of rats were investigated. Results In open-field test, after 2-week intervening with estrogen the locomotor activity and rearing activity of rats in 10μg and 25 μg groups increased compared with 0 μg group. And the sucrose preference index of 10 μg and 25 μg groups increased compared with 0μg group （P〈0.05）, while estrogen 100μg group had no significant difference. In additon, behaviors of PSD rats in forced swimming test went better after 10 μg estrogen. And there was no significant difference among estrogen 25 μg, 100 gg group and 0μg group （P〉0.05）. Immunohistochemical staining indicated that there was no difference of the number of BrdU labeled cells between estrogen 0 μg group and the control group in the SVZ （P〉0.05）. And the number of BrdU positive cell significantly increased after 10 gg and 25 μg estrogen treatment compared with 0 μg group（P〈0.05）. Conclusion A moderate amount of estrogen may improve symptoms of depression on PSD rats through increasing neurogenesis.