Chang Chen-Kuei, Chang Ching-Ping, Liu Shyun-Yeu, Lin Mao-Tsun
Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Prog Brain Res. 2007;162:525-46. doi: 10.1016/S0079-6123(06)62025-6.
When rats were exposed to high environmental temperature (e.g., 42 or 43 degrees C), hyperthermia, hypotension, and cerebral ischemia and damage occurred during heat stroke were associated with increased production of free radicals (specifically hydroxyl radicals and superoxide anions), higher lipid peroxidation, lower enzymatic antioxidant defenses, and higher enzymatic pro-oxidants in the brain of heat stroke-affected rats. Pretreatment with conventional hydroxyl radical scavengers (e.g., mannitol or alpha-tocopherol) prevented increased production of hydroxyl radicals, increased levels of lipid peroxidation, and ischemic neuronal damage in different brain structures attenuated with heat stroke and increased subsequent survival time. Heat shock preconditioning (a mild sublethal heat exposure for 15min) or regular, daily exercise for at least 3 weeks, in addition to inducing overproduction of heat shock protein 72 in multiple organs including brain, significantly attenuated the heat stroke-induced hyperthermia, hypotension, cerebral ischemia and damage, and overproduction of hydroxyl radicals and lipid peroxidation. The precise function of heat shock protein 72 are unknown, but there is considerable evidence that these proteins are essential for survival at both normal and elevated temperatures. They also play a critical role in the development of thermotolerance and protection from oxidative damage associated with cerebral ischemia and energy depletion during heat stroke. In addition, Shengmai San or magnolol (Chinese herbal medicines) or hypervolemic hemodilution (produced by intravenous infusion of 10% human albumin) is effective for prevention and repair of ischemic and oxidative damage in the brain during heat stroke. Thus, it appears that heat shock protein 72 preconditioning induced by prior heat shock or regular exercise training, as well as pretreatment with Shengmai San or magnolol is able to prevent the oxidative damage during heat stroke. On the other hand, hypervolemic hemodilution, Shengmai San, or magnolol is able to treat the oxidative damage after heat stroke onset.
当大鼠暴露于高温环境（如42或43摄氏度）时，中暑期间出现的体温过高、低血压、脑缺血和损伤与自由基（特别是羟基自由基和超氧阴离子）生成增加、脂质过氧化水平升高、酶促抗氧化防御能力降低以及中暑大鼠脑内酶促促氧化剂水平升高有关。用传统的羟基自由基清除剂（如甘露醇或α-生育酚）进行预处理可防止羟基自由基生成增加、脂质过氧化水平升高，减轻中暑时不同脑结构的缺血性神经元损伤，并延长后续存活时间。热休克预处理（15分钟的轻度亚致死性热暴露）或至少持续3周的日常规律运动，除了能在包括脑在内的多个器官中诱导热休克蛋白72过量生成外，还能显著减轻中暑诱导的体温过高、低血压、脑缺血和损伤，以及羟基自由基过量生成和脂质过氧化。热休克蛋白72的确切功能尚不清楚，但有大量证据表明这些蛋白质对于在正常温度和高温下的生存至关重要。它们在热耐受的形成以及预防与中暑期间脑缺血和能量耗竭相关的氧化损伤方面也发挥着关键作用。此外，生脉散或厚朴酚（中药）或高容量血液稀释（通过静脉输注10%人白蛋白产生）对预防和修复中暑期间脑内的缺血性和氧化损伤有效。因此，似乎先前热休克或规律运动训练诱导的热休克蛋白72预处理，以及生脉散或厚朴酚预处理能够预防中暑期间的氧化损伤。另一方面，高容量血液稀释、生脉散或厚朴酚能够治疗中暑发作后的氧化损伤。
