The role of androgen on brain protection by inhalation anestheticsduring cerebral reperfusion

雄激素对脑再灌注时吸入麻醉药脑保护的作用

基本信息

批准号：
22591705
负责人：
UCHIDA Masayoshi
金额：
$ 2.58万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

The diagnosis of perioperative cerebral ischemia is difficult, but the onset of cerebral infarction is fatal. Thus, the prevention of such event is very important for anestheticmanagement. Gender differences are observed in the incidence of cerebral infarction, and generally the incidence of cerebral infarction is less in females than males. It is suggested that the estrogen is strongly involved in this mechanism. On the other hand, there is little information about the role of androgen regarding ischemic events. It hasbeen reported that neuroprotective effect through preconditioning induced by inhalation anesthetic was found only in males, and not seen in females. There is a possibility that the gender difference is involved in the protective effect of inhaled anesthetic for the brain ischemia. Then we intended to investigate the interaction between androgen and sevoflurane regarding cerebral protective effect. Firstly, in order to evaluate thecerebral endothelial function following i … More schemia/reperfusion, we used the closed cranial window preparation associated with the middle cerebral artery occlusion model in the Sprague-Dawley rat. To evaluate the cerebrovascular endothelial function before and after cerebral ischemia/reperfusion, topical administration of acetylcholine could be applied.Unfortunately, by the inhalation of sevoflurane, the attenuation effect of vascular endothelial dysfunction caused by ischemia/reperfusion was not observed.Additionally, we evaluated the tissue oxygen partial pressure of spinal cord (PsptO2) following aortic cross-clamping and -unclamping. In anesthetized rabbits, we prepared for measurement of PsptO2 following aortic cross-clamping using tissue PO2 monitoring. In the experiment, we allocated 18 animals into 3 groups,(d) control group; n=6,(e) estrogen (17β estradiol: 20μg) group; n=6,(f) fulvestrant pretreatment (1mg/kg) groupn=6. Administration of 17β estradiol improved deterioration of the values in PsptO2 at 20 min after aortic cross-clamping and 0, 2, 5 min after aortic unclamp. The improvement was diminished by pretreatment of fulvestrant. Less

围手术期脑缺血的诊断很困难，但脑梗塞的发生是致命的，因此，预防此类事件对于麻醉管理非常重要。雌激素在这一机制中的作用较男性少，但有关雄激素在缺血事件中的作用的信息却很少。吸入麻醉剂诱导的预处理仅在男性中发现，而在女性中未发现。这可能与吸入麻醉剂对脑缺血的保护作用有关。然后我们打算研究雄激素和七氟醚之间的相互作用。首先，为了评估缺血/再灌注后的脑内皮功能，我们使用了与大脑中动脉闭塞模型相关的闭合颅窗制备。为了评估脑缺血/再灌注前后的脑血管内皮功能，可以应用乙酰胆碱局部给药。不幸的是，通过吸入七氟醚，对缺血/再灌注引起的血管内皮功能障碍的减弱作用被削弱。未观察到。此外，我们评估了脊髓组织氧分压（PsptO2）主动脉交叉钳夹和松开。在实验中，我们将 18 只动物分为 3 组，(d) 对照组；(n=6)。 (e)雌激素(17β雌二醇：20μg)组；n=6，(f)氟维司群预处理(1mg/kg)组n=6。给予17β雌二醇改善了主动脉阻断后20分钟和主动脉松开后0、2、5分钟的PsptO2值的恶化，通过改善氟维司群的预处理而减少。