Wang Nien-Lu, Chang Cheng-Kuei, Liou Yann-Lin, Lin Chia-Li, Lin Mao-Tsun
Institute of Physiology, National Yang-Ming University Medical School, Taipei 112, Taiwan.
J Pharmacol Sci. 2005 May;98(1):1-7. doi: 10.1254/jphs.fp0050018. Epub 2005 May 7.
The aim of the present study was to ascertain whether the possible occurrence of overproduction of inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) in the brain and inflammatory cytokines in the peripheral blood exhibited during heat stroke can be reduced by prior administration of Shengmai San, a Chinese herbal medicine. Aminoguanidine, an iNOS inhibitor, was evaluated at the same time as a reference (positive control). Urethane-anesthetized rats were exposed to heat stress (ambient temperature of 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were all significantly lower than in control rats. However, cerebral iNOS immunoreactivity and NO levels were all greater after the onset of heat stroke. The serum levels of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were all increased after the onset of heat stroke. Shengmai San (1.2 g/ml per rat) or aminoguanidine (30 micromol/ml per rat) was administered orally, daily, and consecutively for 7 days before the initiation of heat stress; and this significantly attenuated the heat stress-induced arterial hypotension, cerebral ischemia, and increased levels of brain iNOS-dependent NO production and serum cytokines formation. Shengmai San shared with the aminoguanidine almost the same efficacy in reducing iNOS-dependent NO and cytokines overproduction during heat stroke. These results suggest that Shengmai San or aminoguanidine protects against heat stroke-induced arterial hypotension and cerebral ischemia by inhibition of iNOS-dependent NO overproduction in the brain and excessive accumulation of several inflammatory cytokines in the peripheral blood stream.
本研究的目的是确定预先给予中药生脉散是否可以减少中暑期间大脑中诱导型一氧化氮合酶（iNOS）依赖性一氧化氮（NO）的过量产生以及外周血中炎性细胞因子的出现。同时评估iNOS抑制剂氨基胍作为参考（阳性对照）。用乌拉坦麻醉大鼠，使其暴露于热应激（环境温度43℃）以诱导中暑。对照大鼠暴露于24℃。中暑发作后的平均动脉压和脑血流量均显著低于对照大鼠。然而，中暑发作后，脑iNOS免疫反应性和NO水平均升高。中暑发作后，血清白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α水平均升高。在热应激开始前，每天给大鼠口服生脉散（1.2 g/ml/只大鼠）或氨基胍（30 μmol/ml/只大鼠），连续7天；这显著减轻了热应激诱导的动脉低血压、脑缺血以及脑iNOS依赖性NO产生水平和血清细胞因子形成的增加。生脉散与氨基胍在减少中暑期间iNOS依赖性NO和细胞因子过量产生方面具有几乎相同的功效。这些结果表明，生脉散或氨基胍通过抑制大脑中iNOS依赖性NO的过量产生以及外周血流中几种炎性细胞因子的过度积累，来预防中暑诱导的动脉低血压和脑缺血。
