川芎嗪对药物耳毒性线粒体DNA缺失的影响

摘要

目的研究川芎嗪(TMP)对庆大霉素(GM)导致药物耳毒性豚鼠的线粒体DNA(mtDNA)缺失影响.方法选择体重200-330g健康豚鼠40只,雌雄不拘,随机平均分成正常对照组、GM组、GM+TMP组和TMP组.四组动物混合饲养,每日测量体重调整药量.采用巢式聚合酶链反应检测血液中mtDNA的缺失情况.结果正常对照组和TMP组无mtDNA的缺失,GM组与GM+TMP组均有mtDNA的缺失,GM组mtDNA的缺失率高于GM+TMP组,两组比较差异具有统计学意义(P<0.05).结论庆大霉素可使豚鼠mtDNA发生缺失而引起听力受损；川芎嗪对可以降低mtDNA的缺失,有效地拮抗庆大霉素的耳毒性损伤,改善听力.%　　Objective To investigate the effect of tetramethylpyrazine(TMP) on drug totoxicity of gentamicin(GM) with mtDNA deletion in guinea pigs. Methods Totally 40 healthy guinea pigs, weighing 200-330g, of either gender, were at random divided as normal control group, GM group, TMP+GM group and TMP group, with 10 in each group. Administration was consecutively given for each group, once a day, The body mss was measured every day for regulatingthe dosage. The nested PCR technique was used to test the presence of mtDNA deletion in blood. Results Neither normal control group nor TMP group has mtDNA deletion, both GM group and TMP+GM group have mtDNA deletion. The rate of mtDNA deletion in GM group is higher than that of TMP+GM group, the difference between the two groups is statistically significant(P<0.05). Conclusion GM can induce mtDNA deletion in guinea pigs, resulting in hearing impairment, TMP can reduce mtDNA deletion, effective antagonist of the toxicity of gentamicin ear and improve hearing.