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氟磷酸二异丙酯对清醒、未束缚大鼠体温、心率及运动活动的急性和延迟效应

Acute and delayed effects of diisopropyl fluorophosphate on body temperature, heart rate, and motor activity in the awake, unrestrained rat.

作者信息

Gordon C J

机构信息

Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.

出版信息

J Toxicol Environ Health. 1993 Jun;39(2):247-60. doi: 10.1080/15287399309531749.

Abstract

Acute exposure to diisopropyl fluorophosphate (DFP) causes irreversible inhibition of acetylcholinesterase activity, leading to various behavioral and autonomic sequelae including hypothermia, reduced motor activity, and other neurological dysfunctions. To characterize the acute response and recovery of autonomic and behavioral processes to DFP exposure, rats of the Long-Evans strain were implanted with radiotransmitters that allowed the monitoring of core temperature, heart rate, and motor activity in unrestrained animals 24 h/d. These parameters were monitored for 96 h following subcutaneous injection of DFP at a dose of 0, 0.1, or 1.0 mg/kg. Rats given 0 and 0.1 mg/kg DFP displayed an increase in core temperature and motor activity during the first 24 h postinjection. The 1.0 mg/kg group showed a typical hypothermic response for the first 24 h following DFP administration. Core temperature decreased a maximum of 1.9 degrees C by 5 h after DFP and then started to recover, reaching control levels by 17 h after DFP treatment. Motor activity was also depressed during the first 24-h period in the 1.0 mg/kg group. Heart rate was initially elevated above basal levels in all treatment groups for several hours after treatment, but the 1.0 mg/kg group showed a decrease in heart rate at the time when core temperature began its recovery from hypothermia. Core temperature was the only parameter significantly affected by DFP during the 24-96 h recovery phase. The 0.1 and 1.0 mg/kg groups showed a significant elevation in core temperature for the 3 d after DFP administration. The elevation in core temperature during the recovery from DFP treatment may represent an important facet of the acute cholinergic neurotoxicity of organophosphate compounds.

摘要

急性接触二异丙基氟磷酸酯(DFP)会导致乙酰胆碱酯酶活性的不可逆抑制,引发各种行为和自主神经后遗症,包括体温过低、运动活动减少以及其他神经功能障碍。为了描述自主神经和行为过程对DFP暴露的急性反应和恢复情况,对Long-Evans品系的大鼠植入了无线电发射器,以便在24小时/天的无约束动物中监测核心体温、心率和运动活动。在皮下注射剂量为0、0.1或1.0mg/kg的DFP后,对这些参数进行了96小时的监测。给予0和0.1mg/kg DFP的大鼠在注射后的前24小时内核心体温和运动活动增加。1.0mg/kg组在DFP给药后的前24小时表现出典型的体温过低反应。DFP给药后5小时,核心体温最多下降1.9摄氏度,然后开始恢复,在DFP治疗后17小时达到对照水平。1.0mg/kg组在最初的24小时内运动活动也受到抑制。所有治疗组在治疗后的几个小时内心率最初均高于基础水平,但1.0mg/kg组在核心体温开始从体温过低状态恢复时心率下降。在24 - 96小时的恢复阶段,核心体温是唯一受DFP显著影响的参数。0.1和1.0mg/kg组在DFP给药后的3天内核心体温显著升高。DFP治疗恢复过程中核心体温的升高可能代表了有机磷化合物急性胆碱能神经毒性的一个重要方面。

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