Aminoguanidine protects against intracranial hypertension and cerebral ischemic injury in experimental heatstroke
Aminoguanidine protects against intracranial hypertension and cerebral ischemic injury in experimental heatstroke
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DOI：
10.1254/jphs.95.56
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Lin, MT
中科院分区：
文献类型：
--
作者：
Chang, CP;Lee, CC;Lin, MT
本研究的目的是确定氨基胍是否能减轻实验性中暑时的颅内高压和脑缺血损伤。乌拉坦麻醉大鼠暴露于热应激(环境温度43摄氏度)以诱导中暑。对照组大鼠暴露于24℃。中暑后平均动脉压、脑灌注压和脑血流量均显著低于对照组。而中暑后结肠温度、颅内压、心率、脑组织诱导型一氧化氮合酶(INOS)依赖的NO和神经元损伤评分均高于中暑前。热暴露前30min静脉注射氨基胍(30mumol/kg)可显著减轻中暑引起的体温升高、动脉血压降低、颅内压升高、脑缺血和神经元损伤，并增加脑内iNOS依赖的NO生成。中暑后，下丘脑细胞外缺血标志物(如谷氨酸和乳酸/丙酮酸比值)和损伤标志物(如甘油)浓度也增加。氨基鸟苷预处理显著减轻与中暑相关的下丘脑缺血和损伤标记物的增加。延迟给药(即热暴露开始后0min或30min)可降低对中暑所致体温升高、动脉低血压、颅内高压、脑缺血的预防效果，并增加脑内一氧化氮合酶依赖性NO的生成。这些结果表明，氨基胍通过抑制脑内iNOS依赖的NO的产生，对中暑所致的颅内高压和脑缺血损伤具有保护作用。
The aim of the present study was to ascertain whether aminoguanidine attenuated intracranial hypertension and cerebral ischemic injury in experimental heatstroke. Urethane-anesthetized rats-were exposed to heat stress (ambient temperature of 43degreesC) to induce heatstroke. Control rats were exposed to 24degreesC. Mean arterial pressure, cerebral perfusion pressure, and cerebral blood flow after the onset of heatstroke were all significantly lower than in control rats. However, colonic temperature, intracranial pressure, heart rate, cerebral inducible nitric oxide synthase (iNOS)-dependent NO, and neuronal damage score were greater after the onset of heatstroke. Aminoguanidine (30 mumol/kg, i.v.; 30 min before the start of heat exposure) pretreatment significantly attenuated the heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischemia and neuronal damage, and increased iNOS-dependent NO formation in the brain. The extracellular concentrations of ischemic (e.g., glutamate and lactate/pyruvate ratio) and damage (e.g., glycerol) markers in the hypothalamus were also increased after the onset of heatstroke. Aminoguanidine pretreatment significantly attenuated the increase in hypothalamic ischemia and damage markers associated with heatstroke. Delaying onset of aminoguanidine administration (i.e., 0 or 30 min after the start of heat exposure) reduced the preventive efficiency on heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischemia, and increased NOS-dependent NO formation in brain. These results suggest that aminoguanidine protects against heatstroke-induced intracranial hypertension and cerebral ischemic injury by inhibition of cerebral iNOS-dependent NO production.