褪黑素对顺铂的听觉中枢毒性的影响

THE PROTECTIVE EFFECT OF MELATONIN ON AUDITORY CORTEX TOXICITY INDUCED BY CIS-PLATINUM

目的:研究顺铂的中枢听觉毒性以及褪黑素对其的保护作用。方法:用顺铂和不同浓度褪黑素分别在豚鼠左右腹腔注射7 d后,用分光光度计测量听皮层脑组织LDH活力、MDA、NO含量。结果:顺铂注射7 d后各组的体重均下降,其中以单独注射顺铂组和10 mg.kg-1.d-1褪黑素加顺铂组下降趋势最明显,较处理前有显著差异(P<0.01)。顺铂组动物听皮层LDH活力水平明显高于生理盐水组(P<0.01);褪黑素能显著降低顺铂引起的听皮层脑组织中的LDH增高(P<0.05)。豚鼠腹腔注射顺铂7 d后听皮层MDA含量较腹腔注射生理盐水组明显增高(P<0.01);同时腹腔注射褪黑素能降低听皮层组织MDA含量(P<0.05)。各药物作用后听皮层的NO含量变化统计学比较无显著性意义。结论:腹腔注射顺铂能够作用于听皮层引起细胞损伤。褪黑素对顺铂所致的听皮层细胞损伤有防护作用,机制可能与其抗自由基作用有关。

Aim： To investigate the toxic response in auditory cortex of guinea pigs caused by cis-platinum （DDP）, and the protective role of melatonin in this effect. Methods： Cis-platinum and melatonin were injected peritoneally. LDH, MDA, NO in the auditory cortex were detected by spectrophotometer. Results： The body weight of the guinea pigs was diminished by peritoneal injection of Cis-platinum for 7 days （ P 〈 0.01）. Peritoneal injection of Cis-platinum induced the increased leakage of LDH （P 〈 0.05 vs injection of normal saline）. This effect was reduced by injection of MT （ P 〈 0.05）. The content of MDA in the auditory cortex was also increased because of injection of Cis-platinumv for 7 days （ P 〈 0.01） and MT reduced this effect （ P 〈 0.05）. The change of NO in the auditory cortex was not statistically significant after injection of Cis-platinum or Cis-platinum with MT. Conclusion： Peritoneal injection of Cis-platinum could destroy neurons in the auditory cortex. This effect could be reduced by melatonin by an anti-free radials mechanism.