权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

RESEARCH OF THE MECHANISM OF GENEKRAL ANESTHESIA-ROLE OF P-GLYCOPROTEIN

全麻机制研究——P-糖蛋白的作用

基本信息

批准号：
14571460
负责人：
ODA Yutaka
金额：
$ 2.05万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571460/
关键词：
P-GLYCOPROTEIN OUINIDINE LIDOCAINE BUPIVACAINE LOCAL ANESTHETICS CONVULSIONS DEXMEDETOMIDINE

项目摘要

P-glycoprotein is expressed in endothelial cells in the blood brain barrier (BBB), intestinal mucosa and various other organs. P-glycoprotein expressed in BBB exports various compound administered extracorporeally. Intravenously administered local anesthetics are delivered to the central nervous system, promoting excitation and convulsion. Local anesthetics in the brain are also involved in the cardiovascular toxicity. For elucidating the role of P-glycoprotein for controlling convulsions by local anesthetics, we have developed an awake, spontaneously breathing rat model for observing convulsions.Male Sprague-Dawley rats aged 9-10 weeks and weighing 350-400g were housed 12 hour dark and light cycle. On the day of experiment, rat was anesthetized with inhalational sevoflurane in oxygen. Polyethylene catheters (PE-50 and SP-3) were inserted into carotid artery and cervical vein, respectively. After emergence from anesthesia, lidocaine was intravenously administered at 4 mg/kg/min under t … More he monitoring of blood pressure and heart rate until tonic/clonic convulsions occurred. At the onset of convulsions, rats were killed by intravenous administration of thiopental and the brain was perfused from the aorta. Blood sample was obtained from the indwelling arterial catheter and plasma and brain concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) were measured. The same experimental protocol was used for measuring the convulsive potency of racemic bupivacaine (bupivacaine). Plasma concentrations of lidocaine and bupivacaine were measured according to our previous study. We have developed a new method for simple measurement of the concentration of local anesthetics in brain homogenates.Convulsant potency of lidocaine was not affected by pretreatment of a P-glycoprotein, quinidine. Convulsive dose and the concentration of bupivacaine in the brain were not changed by quinidine ; however, plasma concentration of bupivacaine at the onset of convulsinsions was significantly decreased by quinidine. These results suggest that P-glycoprotein is involved in controlling the concentration of bupivacaine, but not lidocaine, in the brain. Less

P-糖蛋白在血脑屏障（BBB）、肠粘膜和各种其他器官的内皮细胞中表达。血脑屏障中表达的P-糖蛋白输出体外给药的各种化合物。颅内给药的局部麻醉药被输送到中枢神经系统，促进兴奋和惊厥。脑内局部麻醉药也参与心血管毒性。为了阐明P-糖蛋白在局麻药控制惊厥中的作用，我们建立了一种清醒、自主呼吸的大鼠惊厥模型，将9-10周龄、体重350- 400克的雄性Sprague-Dawley大鼠置于12小时明暗循环中。实验当天，用吸入性七氟醚在氧气中麻醉大鼠。将聚乙烯导管（PE-50和SP-3）分别插入颈动脉和颈静脉。麻醉苏醒后，在麻醉诱导下以4 mg/kg/min的速度静脉注射利多卡因， ...更多信息监测血压和心率，直至发生强直性/阵挛性惊厥。在惊厥发作时，通过静脉注射硫喷妥钠处死大鼠，并从主动脉灌注脑。从留置的动脉导管中采集血样，测定利多卡因及其主要代谢产物单乙基甘氨酸二甲叉酯（MEGX）的血浆和脑浓度。相同的实验方案用于测量外消旋布比卡因（布比卡因）的惊厥效力。利多卡因和布比卡因的血药浓度根据我们以前的研究。我们建立了一种简便测定脑组织匀浆中局麻药浓度的新方法，P-糖蛋白奎尼丁对利多卡因的致惊厥作用无影响。惊厥剂量和布比卡因在大脑中的浓度没有改变奎尼丁，但是，血浆浓度的布比卡因在惊厥发作时，奎尼丁显着降低。这些结果表明，P-糖蛋白参与控制布比卡因的浓度，而不是利多卡因，在大脑中。少