Obana W G, Pitts L H, Nishimura M C
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.
J Neurosurg. 1988 Jul;69(1):98-103. doi: 10.3171/jns.1988.69.1.0098.
The authors examined the effect of the opiate antagonists naloxone and thyrotropin-releasing hormone (TRH) on neurological outcome and the size of areas of cerebral infarction in a rat model of focal cerebral ischemia. The middle cerebral artery (MCA) was permanently occluded in 66 adult Sprague-Dawley rats. The rats were randomly divided into three groups. In 20 Group I rats, TRH in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2 mg/kg/hr for 4 hours. In 20 Group II rats, naloxone in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2-mg/kg/hr for 4 hours. In 26 Group III rats, physiological saline was administered as an initial 0.5-cc bolus followed by continuous infusion of 0.5 cc/hr for 4 hours. All solutions were given in volumes of 0.5 cc for the bolus and 0.5 cc/hr for continuous infusion, and all infusions were begun within 10 minutes of MCA occlusion. Twenty-four hours after treatment, the rats underwent a careful neurological examination and were then sacrificed immediately. The size of areas of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride staining techniques. The neurological grade of the rats correlated with the size of infarcted areas among all grades, irrespective of treatment (p less than 0.01). Neither naloxone nor TRH improved neurological function or reduced the size of infarction compared to saline-treated control rats. Treatment with TRH caused a significant increase in mean arterial blood pressure during infusion, but naloxone had no effect. These results suggest that neither TRH nor naloxone are effective in the treatment of acute focal cerebral ischemia.
作者在局灶性脑缺血大鼠模型中研究了阿片类拮抗剂纳洛酮和促甲状腺激素释放激素（TRH）对神经功能转归及脑梗死面积大小的影响。66只成年Sprague-Dawley大鼠的大脑中动脉（MCA）被永久性阻断。大鼠被随机分为三组。20只I组大鼠，最初以2mg/kg的剂量静脉推注生理盐水溶解的TRH，随后以2mg/kg/小时的速度持续输注4小时。20只II组大鼠，最初以2mg/kg的剂量静脉推注生理盐水溶解的纳洛酮，随后以2mg/kg/小时的速度持续输注4小时。26只III组大鼠，最初以0.5cc的剂量静脉推注生理盐水，随后以0.5cc/小时的速度持续输注4小时。所有溶液推注量为0.5cc，持续输注速度为0.5cc/小时，所有输注均在MCA阻断后10分钟内开始。治疗24小时后，对大鼠进行仔细的神经学检查，然后立即处死。采用2,3,5-氯化三苯基四氮唑染色技术评估脑梗死面积大小。所有分级的大鼠神经学分级与梗死面积大小相关，与治疗无关（p<0.01）。与生理盐水处理的对照大鼠相比，纳洛酮和TRH均未改善神经功能或减小梗死面积。TRH治疗在输注期间导致平均动脉血压显著升高，但纳洛酮无此作用。这些结果表明，TRH和纳洛酮均对急性局灶性脑缺血治疗无效。
