Hoogeveen J F, Van Der Kracht A H, Wondergem J, Gonzalez Gonzalez D, Haveman J
Department of Radiotherapy, University of Amsterdam, Academish Medisch Centrum, The Netherlands.
Neurotoxicology. 1993 Spring;14(1):1-7.
The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally heated at a temperature of 45 degrees C (5-30 min). Loss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was significantly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cisplatin treated rats were more sensitive to heat than nerves from control rats (dose modifying factor = 1.5 +/- 0.2). Histopathological investigation of nerves after heat alone or after heat preceded by cisplatin confirmed these differences and showed that edema, vascular damage and axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies showed that cisplatin treatment before hyperthermia caused a delay in recovery from motor function loss of about 6 days. Cisplatin treatment after hyperthermia had no influence on recovery from motor function loss.
研究了顺铂对大鼠坐骨神经局部热敏感性的影响。大鼠腹腔注射1.7mg/kg顺铂，每周两次，共6周，累积剂量达20.4mg/kg。顺铂治疗结束后，将5mm长的神经节段局部加热至45℃（5 - 30分钟）。加热24小时后，通过趾展试验评估运动功能丧失情况。计算得出对照神经的半数有效剂量（ED50）显著（p < 0.01）大于顺铂处理大鼠的ED50；分别为16.3±1.1分钟和10.9±1.1分钟。这表明顺铂处理大鼠的神经比对照大鼠的神经对热更敏感（剂量修正因子 = 1.5±0.2）。对单纯加热或顺铂预处理后加热的神经进行组织病理学研究证实了这些差异，并表明与对照神经相比，在较低热剂量下就会出现水肿、血管损伤以及轴突和髓鞘的轴突变性改变。恢复研究表明，热疗前的顺铂治疗导致运动功能丧失的恢复延迟约6天。热疗后的顺铂治疗对运动功能丧失的恢复没有影响。
