Zeynalov Emil, Rezvani Niloofar, Miyazaki Chikao, Liu Xiaoguang, Littleton-Kearney Marguerite T
Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2014 Jul 10;9(7):e102194. doi: 10.1371/journal.pone.0102194. eCollection 2014.
Several studies demonstrate that estrogen treatment improves cerebral blood flow in ischemic brain regions of young ovariectomized (OVX) rats. Estrogen receptor-α (ER-α) may mediate estrogen's beneficial actions via its effects on the cerebral microvasculature. However, estrogen-derived benefit may be attenuated in aged, reproductively senescent (RS) rats. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-α and ER-β.
Fisher-344 (n = 37) female rats were randomly divided into the following groups: OVX, OVX CE-treated, RS untreated, and RS CE-treated. After 30 days pretreatment with CE (0.01 mg/kg) rats were subjected to 15 min. transient global cerebral ischemia. Non-ischemic naïve, OVX and RS rats were used as controls. Expression of ER-α and ER-β in isolated cortical cerebral microvessels (20 to 100 µm in diameter) was assessed using Western blot and immunohistochemistry techniques.
Age and reproductive status blunted nonischemic ER-α expression in microvessels of OVX rats (0.31 ± 0.05) and RS rats (0.33 ± 0.06) compared to naïve rats (0.45 ± 0.02). Postischemic microvascular expression of ER-α in OVX rats (0.01 ± 0.0) was increased by CE treatment (0.04 ± 0.01). Expression of ER-α in microvessels of RS rats (0.03 ± 0.02) was unaffected by CE treatment (0.01 ± 0.02). Western blot data are presented as a ratio of ER-α or ER-β proteins to β-actin and. Oral CE treatment had no effect on ER-β expression in postischemic microvessels of OVX and RS rats. Statistical analysis was performed by One-Way ANOVA and a Newman-Keuls or Student's post-hoc test.
Chronic treatment with CE increases ER-α but not ER-β expression in cerebral microvessels of OVX rats. Aging appears to reduce the normal ability of estrogen to increase ER-α expression in postischemic cerebral microvessels.
多项研究表明，雌激素治疗可改善年轻去卵巢（OVX）大鼠缺血脑区的脑血流量。雌激素受体-α（ER-α）可能通过其对脑微血管的作用介导雌激素的有益作用。然而，在衰老的生殖衰老（RS）大鼠中，雌激素带来的益处可能会减弱。我们的目标是确定衰老、雌激素缺乏以及口服结合雌激素（CE）进行雌激素补充对缺血后脑微血管中ER-α和ER-β蛋白表达的影响。
将37只Fisher-344雌性大鼠随机分为以下几组：OVX组、OVX CE治疗组、RS未治疗组和RS CE治疗组。在用CE（0.01 mg/kg）预处理30天后，大鼠经历15分钟的短暂全脑缺血。未经历缺血的正常、OVX和RS大鼠用作对照。使用蛋白质印迹法和免疫组织化学技术评估分离的皮质脑微血管（直径20至100μm）中ER-α和ER-β的表达。
与正常大鼠（0.45±0.02）相比，年龄和生殖状态使OVX大鼠（0.31±0.05）和RS大鼠（0.33±0.06）微血管中的非缺血性ER-α表达减弱。CE治疗使OVX大鼠缺血后微血管中ER-α的表达增加（从0.01±0.0增加到0.04±0.01）。RS大鼠微血管中ER-α的表达（0.03±0.02）不受CE治疗影响（0.01±0.02）。蛋白质印迹数据以ER-α或ER-β蛋白与β-肌动蛋白的比率表示。口服CE治疗对OVX和RS大鼠缺血后微血管中ER-β的表达没有影响。采用单因素方差分析和Newman-Keuls或Student事后检验进行统计分析。
CE长期治疗可增加OVX大鼠脑微血管中ER-α的表达，但不增加ER-β的表达。衰老似乎会降低雌激素增加缺血后脑微血管中ER-α表达的正常能力。
