Toung Thomas J, Chen Tsung-Ying, Littleton-Kearney Marguerite T, Hurn Patricia D, Murphy Stephanie J
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Cereb Blood Flow Metab. 2004 Oct;24(10):1160-6. doi: 10.1097/01.WCB.0000135594.13576.D2.
Recent data from the Women's Health Initiative have highlighted many fundamental issues about the utility and safety of long-term estrogen use in women. Current hormone replacement therapy for postmenopausal women incorporates progestin with estrogen, but it is uncertain if combined therapy provides major cerebrovascular risks or benefits to these women. No experimental animal stroke studies have examined combined hormone administration. The authors tested the hypothesis that combined hormone treatment reduces ischemic injury in middle-aged female rat brain. Reproductively senescent female rats underwent 2-hour middle cerebral artery occlusion (MCAO) followed by 22 hours reperfusion. Estrogen implants were placed subcutaneously at least 7 days before MCAO, and progesterone intraperitoneal injections were given 30 minutes before MCAO, at initiation, and at 6 hours of reperfusion. Rats received no hormone, a 25-microg estrogen implant, a 25-microg estrogen implant plus 5 mg/kg intraperitoneal progesterone, or 5 mg/kg intraperitoneal progesterone. Cortical, caudoputamen, and total infarct volumes were assessed by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis at 22 hours reperfusion. Cortical and total infarct volumes, except in the acute progesterone-treated group, were significantly attenuated in all estrogen-alone and combined hormone-treated groups. There were no significant differences in caudoputamen infarct volumes in all hormone-treated groups as compared with untreated rats. These data have potential clinical implications relative to stroke for postmenopausal women taking combined hormone replacement therapy.
妇女健康倡议组织的最新数据凸显了许多关于女性长期使用雌激素的效用和安全性的基本问题。目前用于绝经后女性的激素替代疗法是将孕激素与雌激素联合使用，但这种联合疗法是否会给这些女性带来重大的脑血管风险或益处尚不确定。尚无实验动物中风研究对联合激素给药进行过检测。作者检验了联合激素治疗可减轻中年雌性大鼠脑缺血损伤这一假设。处于生殖衰老期的雌性大鼠接受了2小时的大脑中动脉闭塞（MCAO），随后再灌注22小时。在MCAO至少7天前皮下植入雌激素，并在MCAO前30分钟、开始时以及再灌注6小时时腹腔注射孕激素。大鼠分别接受无激素处理、植入25微克雌激素、植入25微克雌激素加腹腔注射5毫克/千克孕激素或腹腔注射5毫克/千克孕激素。在再灌注22小时时，通过2,3,5-三苯基氯化四氮唑染色和数字图像分析评估皮质、尾壳核和总梗死体积。除急性孕激素治疗组外，所有单独使用雌激素和联合激素治疗组的皮质和总梗死体积均显著减小。与未治疗的大鼠相比，所有激素治疗组的尾壳核梗死体积均无显著差异。这些数据对于接受联合激素替代疗法的绝经后女性中风具有潜在的临床意义。
