胆碱能阻滞剂对毒死蜱引起大鼠体温改变的影响与尾部散热变化的关系

Effect of cholinergic antagonists on organophosphate pesticide chlorpyrifos induced changes in body temperature in the rat and its relationship with change in the heat loss from the tail

目的本研究探讨中枢和外周胆碱能阻滞剂对有机磷杀虫剂毒死蜱(CHP)引起的低温效应和延迟发热反应的影响与尾部散热变化的关系。方法用无线遥测技术连续记录25℃环境中大鼠的体核温度,用数字体温计测量尾部皮肤温度,每次间隔1h。在CHP(25mg/kg)引起大鼠低温期和延迟性发热期,分别给外周胆碱能阻滞剂甲基东莨菪碱(1mg/kg)和中枢胆碱能阻滞剂东莨菪碱(1mg/kg)。结果①毒死蜱导致体温快速降低时,伴有尾部散热反应明显增加。东莨菪碱可以阻滞CHP的降温作用和血管舒张效应,但甲基东莨菪碱对其无明显影响。②甲基东莨菪碱可阻滞CHP引起的延迟发热反应,而东莨菪碱可轻度提高其发热反应。结论CHP引起的低温和血管舒张反应主要是通过中枢胆碱能通路所致,而发热反应主要是通过外周胆碱能通路所引起。实验对人暴露在有机磷杀虫剂中出现的持续发热现象和使用阿托品治疗提供了一种可能的解释,对其发热的治疗用外周胆碱能阻滞剂甲基东莨菪碱可能疗效更好。

Objective To utilize cholinergic antagonists to examine the mechanism of action of the hypothermia and delayed febrile response to the organophosphate pesticide chlorpyrifos and its relationship with change in the heat loss from the tail. Methods Core temperature was monitored by telemetry in female rats maintained at an ambient temperature of 25 ℃. Tail skin temperature was measured at 1 h intervals with digital thermometer. The peripheral cholinergic antagonist, methylscopolamine （1 mg/kg ） and central cholinergic antagonist, scopolamine （ 1 mg/kg ） were administered during the period of chlorpyrifos （25 mg/kg） induced hypothermia and hyperthermia. Results （1）Chlorpyrifos led to a rapid reduction in core temperature concomitant with a marked elevation in the heat loss from the tail. The hypothermia and vasodilatory effects of ehlorpyrifos were blocked by administration of scopolamine, but not by methylseopolamine. （2）The delayed fever response was augmented by scopolamine but blocked by methyl- scopolamine. Conclusion The results indicate that organophosphatc pesticide chlorpyrifos - induced hypothermia and vasodilatory response are mediated primarily through a central cholinergie pathway. Fever response is mediated primarily through a peripheral eholinergic pathway. On the other hand, the data provides a possible explanation for the persistent fever in human exposed to organophosphate pesticides and treated with atropine. Methyl scopolamine may be a more effective therapy in the treatment of the fever.