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小鼠乙醇致死率的温度依赖性

Temperature dependence of ethanol lethality in mice.

作者信息

Malcolm R D, Alkana R L

出版信息

J Pharm Pharmacol. 1983 May;35(5):306-11. doi: 10.1111/j.2042-7158.1983.tb02939.x.

Abstract

The present study provides systematic evidence indicating a direct relationship between environmental temperature, rectal temperature and ethanol lethality. Male, C57 BL/6J mice, previously housed at room temperature (23 +/- 1 degree C), were injected intraperitoneally with 4.8 to 9.2 g kg-1 ethanol and then exposed for 24 h to ambient temperatures that did not appreciably exceed the thermally neutral range for sober mice (20 to 35 degrees C). There was a direct relationship between temperature and ethanol lethality at 8 and 24 h after injection. The 8 h LD50 increased by 64%, from 5.3 to 8.7 g kg-1, as environmental temperature decreased from 35 to 20 degrees C. The 24 h LD50 increased by 51%, from 5.3 to 8.0 g kg-1, across this temperature range. Each 5 degrees C reduction in ambient temperature induced a significant decrease in the rectal temperature of ethanol-injected mice. Mean rectal temperature ranged from 2.2 degrees C above baseline at an ambient temperature of 35 to 15 degrees C below baseline in the 20 degrees C environment. Ethanol induced a significant dose-related hypothermia in mice exposed to the 20, 25 and 30 degrees C environments but did not produce hypothermia in animals kept in the 35 degrees C environment. These findings indicate that the potency of potentially lethal ethanol doses varies with body temperature in accordance with partition and membrane expansion-fluidization theories of anaesthesia.

摘要

本研究提供了系统性证据,表明环境温度、直肠温度与乙醇致死率之间存在直接关系。将先前饲养在室温(23±1℃)下的雄性C57 BL/6J小鼠腹腔注射4.8至9.2 g kg-1乙醇,然后在不明显超过清醒小鼠热中性范围(20至35℃)的环境温度下暴露24小时。注射后8小时和24小时,温度与乙醇致死率之间存在直接关系。随着环境温度从35℃降至20℃,8小时半数致死剂量(LD50)增加了64%,从5.3 g kg-1增至8.7 g kg-1。在此温度范围内,24小时LD50增加了51%,从5.3 g kg-1增至8.0 g kg-1。环境温度每降低5℃,注射乙醇小鼠的直肠温度就会显著下降。平均直肠温度范围从环境温度为35℃时比基线高2.2℃到20℃环境中比基线低15℃。乙醇在暴露于20℃、25℃和30℃环境的小鼠中诱导出显著的剂量相关体温过低,但在饲养于35℃环境的动物中未产生体温过低。这些发现表明,根据麻醉的分配和膜膨胀-流化理论,潜在致死乙醇剂量的效力随体温而变化。

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