Tsai Cheng-Chia, Lin Mao-Tsun, Yang Chia-Chang, Liao Jyh-Fei, Lee Jie-Jen
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Shock. 2006 Dec;26(6):601-7. doi: 10.1097/01.shk.0000230298.01387.d8.
The present study was performed to assess the prophylactic effect of platonin, a cyanine photosensitizing dye and an inhibitor of proinflammatory cytokines, in an animal model of heatstroke. Anesthetized rats were immediately divided into 2 major groups after the start of heat stress and administered either isotonic sodium chloride solution (dose, 1 mL/kg of body weight i.v.) or platonin (dose, 12.5-50 microg/mL per kilogram of body weight i.v.). They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the isotonic sodium chloride solution-pretreated rats underwent heat stress, their survival time values were found to be from 20 to 24 min. Pretreatment with intravenous doses of platonin (12.5-50 microg/mL per kilogram of body weight) immediately after the start of heat exposure significantly improved survival time during heatstroke (duration, 63-185 min). As compared with normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of creatinine, serum urea nitrogen, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time and D-dimer in the plasma, cellular ischemia and injury markers in striatum, and intracranial pressure. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, brain Po2, and platelet count and protein C in the plasma. Immediately after the start of heat exposure, the previous administration of platonin significantly improved survival time by reducing the systemic inflammation, hypercoagulable state, and tissue ischemia and damage during heatstroke. The results demonstrate that platonin is effective for attenuation of heatstroke reactions.
本研究旨在评估花青素类光敏染料及促炎细胞因子抑制剂铂洛通（platonin）在中暑动物模型中的预防作用。热应激开始后，将麻醉的大鼠立即分为两大组，分别静脉注射等渗氯化钠溶液（剂量为1 mL/kg体重）或铂洛通（剂量为每千克体重12.5 - 50 μg/mL）。使它们暴露于43℃的环境温度以诱导中暑。另一组大鼠暴露于室温（26℃）作为正常体温对照。持续监测它们的生理和生化参数。当用等渗氯化钠溶液预处理的大鼠遭受热应激时，发现其存活时间为20至24分钟。热暴露开始后立即静脉注射铂洛通（每千克体重12.5 - 50 μg/mL）预处理可显著提高中暑期间的存活时间（持续时间为63 - 185分钟）。与正常体温对照相比，所有用赋形剂预处理的中暑动物血浆中的肌酐、血清尿素氮、碱性磷酸酶、天冬氨酸转氨酶、丙氨酸转氨酶、肿瘤坏死因子α、凝血酶原时间、活化部分凝血活酶时间和D - 二聚体水平更高，纹状体中的细胞缺血和损伤标志物以及颅内压也更高。相反，所有用赋形剂预处理的中暑动物的平均动脉压、脑灌注压、脑血流量、脑氧分压以及血浆中的血小板计数和蛋白C水平较低。热暴露开始后立即给予铂洛通可通过减轻中暑期间的全身炎症、高凝状态以及组织缺血和损伤，显著提高存活时间。结果表明铂洛通对减轻中暑反应有效。
