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异丙嗪对家兔EGTA性发热的解热作用及其机制研究

王彦平 王华东 陈小琳 陆大祥 李楚杰 颜亮

  摘 要 目的:观察异丙嗪(promethazine,PMZ)对家兔EGTA性发热的影响并探讨其作用机制。方法:侧脑室和静脉给药。用Fura-2荧光分光光度法测定细胞内游离钙浓度([Ca2+]i)。结果:(1)侧脑室灌注0.6 μmol EGTA引起家兔明显的发热反应,侧脑室灌注0.6 μmol EGTA 20 min 后,静脉注射PMZ(5 mg/kg)明显抑制EGTA引起的结肠温度上升,其3 h发热反应指数明显低于侧脑室灌注0.6 μmol EGTA 20 min后静脉注射生理盐水(NS)组。而侧脑室灌注人工脑脊液(ACSF)20 min后静脉注射PMZ(5 mg/kg)组家兔结肠温度明显低于ACSF+NS对照组。(2)体外实验发现,向下丘脑细胞悬液中加入终浓度为0.74 mmol/L的PMZ,下丘脑细胞[Ca2+]i从(159.2±18.8)nmol/L升高到(533.7±90.1)nmol/L(P<0.05)。 结论:PMZ诱导体温调节中枢神经细胞[Ca2+]i升高可能是PMZ抑制家兔EGTA性发热的中枢机制之一。
  主题词 依他酸;发热;钙;异丙嗪

The antipyretic effect of promethazine on egtazic acid-induced fever in rabbits

WANG Yan-Ping,WANG Hua-Dong,LU Da-Xiang,CHEN Xiao-Lin,LI Chu-Jie,YAN Liang
Dept.of Pathophysiology,Jinan University Medical College,Guangzhou(510632)

  Abstract AIM:To investigate the effect of promethazine(PMZ)on egtazic acid-induced fever in rabbits and its mechanism.METHODS:Egtazic acid was administrated intracerebroventricularly,PMZ was given intravenously.Free Ca2+ intracellular concentrations([Ca2+]i)was measured by Fura-2 fluorometry.RESULTS:(1)0.06 μmol egtazic acid intracerebroventricularly infused induced a rise in colonic temperature,when PMZ(5 mg/kg) was administrated intravenously 20 min after the infusion of egtazic acid,it reduced the febrile responses of rabbits to egtazic acid significantly (0.06 μmol) but without complete suppression.PMZ administrated alone caused a marked decrease in colonic temperature.(2)PMZ (0.74 mmol/L) increased [Ca2+]i in hypothalamus cells from(159.2±18.8)nmol/L to(533.7±90.1)nmol/L (P<0.05).CONCLUSION:PMZ possesses antipyretic effect on egtazic acid-induced fever in the rabbit and raises the possibility that the antipyretic actions of PMZ are mediated through the increase of [Ca2+]i incuced by PMZ.
  MeSH Egtazic acid;Fever;Calcium;Promethazine

  组胺H1受体阻断剂异丙嗪(promethazine,PMZ)是一种常用的抗过敏药物,它具有降低正常体温和抑制家兔内毒素性

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