东莨菪碱和甲基东莨菪碱对毒死蜱引起大鼠体温变化的影响与尾部散热变化的关系

Effect of Scopolamine and Methylscopolamine on Organophosphate Pesticide Chlorpyrifos Induced Changes in Body Temperature in the Rat and Its Relationship with Change in the Heat Loss from the Tail

目的本研究是探讨东莨菪碱和甲基东莨菪碱对有机磷杀虫剂毒死蜱(CHP)引起的低温效应和延迟性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℃环境温度中大鼠的体核温度,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断剂甲基东莨菪碱(1mg/kg)和中枢周胆碱能阻断剂东莨菪碱(1mg/kg)。结果毒死蜱导致体温快速的降低时,伴有尾部散热反应明显增加。东莨菪碱可以阻断CHP的降温作用和血管舒张效应,但甲基东莨菪碱对其作用无明显影响。甲基东莨菪碱可可阻断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。结论实验结果证明,有机磷杀虫剂毒死蜱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断剂甲基东莨菪硷可能疗效更好。

Objective To utilize scopolamine and methylscopolamine to examine the mechanism of the 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 60min intervals with digital thermometer. The peripheral cholinergic antagonist, methylscopolamine （1mg/kg） and central cholinergic antagonist, scopolamine （1mg/kg） were administered during the period of hypothermia and hyperthermia which were induced by chlorpyrifos （25mg/kg） induced. Results Chlorpyrifos led to a rapid reduction in core temperature accompanied with a marked elevation in the heat loss from the tail. The hypothermia and vasodilatory effects of chlorpyrffos were blocked by administration of scopolamine, but not by methylscopolamine. The delayed fever response was augmented slightly by scopolamine but blocked by methylscopolamine. Conclusion The results indicate that organophosphate pesticide chlorpyrifos - induced hypothermia and vasodilatory response are mediated primarily through a central cholinergic pathway. Fever response is mediated primarily through a peripheral cholinergic 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.