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阿司匹林对中暑休克大鼠的保护及抗疲劳作用

陈爱华, 宋旭东, 罗炳德, 邹飞

南方医科大学珠江医院心内科. 广州 510282；南方医科大学高温医学研究所. 广州 510515

摘要

本研究旨在探讨阿司匹林是否可以通过降低中暑休克大鼠的白介素-1β (interleukin-1β, IL-1β)水平从而发挥抗中暑休克作用。研究包括：(1)预先给予阿司匹林对大鼠中暑休克的影响；(2)特异性一氧化氮合酶(inducible nitric oxide synthase, iNOS)抑制剂氨基胍(aminoguanidine, AG)对大鼠中暑休克的影响；(3)预先给予阿司匹林对清醒大鼠抗高温疲劳的影响。通过将大鼠 置于仿真模拟高温气候舱接受环境高温(环境温度 41℃，相对湿度 65%)热暴露以诱导中暑休克，建立中暑休克动物模型。实验(1)和(2)分别将大鼠随机分为对照组和阿司匹林处理组，或对照组和AG组，记录热暴露过程中平均动脉压(mean arterial blood pressure, MAP)，结肠温度(colonic temperature, Tco)，心电图(electrocardiograph, ECG)，检测血浆IL-1β或NO浓度。实验(3)将对照组和阿司匹林处理组清醒大鼠置于水温41℃的水箱中，自由游泳，记录生存时间。结果显示，预先给予阿司匹林对 大鼠中暑休克形成后血压下降有显著的抑制作用并延长生存时间，抑制血浆IL-1β升高的程度，但对体温变化没有显著影响。预先给予阿司匹林显著延长清醒大鼠在高温疲劳条件下生存时间。AG可以抑制中暑休克形成后大鼠MAP下降并显著延长大 鼠生存时间，而且可以显著抑制热暴露后大鼠血浆NO浓度上升，但对大鼠热暴露后体温变化没有显著影响。结果提示，IL- 1β可能通过诱导iNOS降低外周血管张力从而参与中暑休克形成，预防性给予抗炎剂量阿司匹林可能对中暑休克出现的血压降低有一定的保护，同时增强对高温及疲劳耐受性，这种影响可能是通过对IL-1β以及局部iNOS的抑制而实现的。

关键词： 中暑休克; 白细胞介素-1β; 阿司匹林; 抗疲劳; 血压

Protective and anti-fatigue effects of aspirin against heatstroke in rats

Chen Aihua, Song Xudong, Luo Bingde, Zou Fei

Department of Cardiology, Zhujiang Hospital, Southern Medical University. Guangzhou 510282, China；Institute of High Temperature Medicine, Southern Medical University, Guangzhou 510515, China

Abstract

The purpose of this study is to determine whether aspirin can reduce interleukin-1β (IL-1β) concentration and exert protective effects against heatstroke. The heatstroke rat model was established through exposing rat to a high ambient temperature (HAT, Ta 41℃, relative humidity 65%) in a simulative HAT chamber to induce heatstroke. Three parts were performed in the present experiment: (1) To determine the effects of pretreatment with aspirin against heatstroke; (2) To prove the effects of specifically reducing inducible nitric oxide synthase (iNOS) against rat heatstroke by iNOS selective prohibitor aminoguanidine (AG); (3) To determine the effects of aspirin against heatstroke and fatigue. In part 1 and 2, Sprague-Dawley rats were randomly assigned to control and aspirin groups or AG groups respectively. Mean arterial blood pressure (MAP), colonic temperature (Tco), electrocardiograph (ECG) were monitored during heat exposure (HE) and blood samples were taken 0 and 60 min after HE for IL-1β assay or nitric oxide (NO) assay. In part 3, additional control and aspirin groups of conscious rats were put in a barrel with 41℃ water and kept swimming until drowning over 10 s, and then intervals were recorded as survival time. The results from part 1 showed that from 0 to 50 min after HE, MAPs of control group and aspirin group were not significantly different. About 50~60 min after HE, MAPs of both groups were decreased abruptly and MAPs of control group were decreased significantly in comparison with those of aspirin group. Tco of both groups was increased until to 42℃, without significant difference. Time of heatstroke onset was not significantly different, while survival time was significantly longer in aspirin group than that in control group. Plasma IL-1β concentrations in both groups were significantly increased after HE, and the concentration was significantly higher in the control group than that in aspirin group 60 min after HE. In part 3, the survival time was significantly longer in aspirin group than that in control group. In part 2, MAPs of both groups from 0 to 50 min after HE were not significantly different, whereas 55~60 min after HE, MAPs of control group were decreased significantly in comparison with those of AG group; Tco of both groups was increased after HE until to 42℃, but without significant difference. The time of the heatstroke onset and survival time of AG group were significantly longer than that of control group; the plasma NO concentrations of two groups were significantly higher 60 min after HE than those 0 min after HE, and the plasma NO concentration of control group was significantly higher than that of AG group 60 min after HE. In conclusion, IL-1β may contribute to heatstroke through inducing iNOS, which attenuates the tone of peripheral blood vessel, and pretreatment with aspirin can provide preventive effects against heatstroke and reinforce the heat and fatigue endurance, which may be associated with inhibition of systemic IL-1β levels and local iNOS levels.

Key words: Hheatstroke;Interleukin-1β;Aspirin;Anti-fatigue;Blood pressure

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引用本文：

陈爱华, 宋旭东, 罗炳德, 邹飞. 阿司匹林对中暑休克大鼠的保护及抗疲劳作用 [J]. 生理学报 2005; 57 (4): .

Chen Aihua, Song Xudong, Luo Bingde, Zou Fei. Protective and anti-fatigue effects of aspirin against heatstroke in rats. Acta Physiol Sin 2005; 57 (4): (in Chinese with English abstract).