川芎嗪对顺铂耳毒性保护作用的实验研究

The study on protection of ligustrazine against cisplatin-induced ototoxicity

目的探讨活血化瘀中药川芎嗪是否对顺铂的耳毒性具有保护作用。方法将听力正常的30只豚鼠随机分为3组,每组10只。对照组:生理盐水3 ml/(kg.d)腹腔注射6天;顺铂组:顺铂3 mg/(kg.d)腹腔注射6天;顺铂加川芎嗪组:先腹腔注射川芎嗪140 mg/(kg.d)3天,从第4天起腹腔注射川芎嗪140 mg/(kg.d)后再注射顺铂3 mg/(kg.d)6天。给药前后通过听觉脑干诱发电位(ABR)检测豚鼠听功能的变化;然后在麻醉状态下断头取耳蜗,半数标本切片后用DNA末端转移酶介导的缺口末端标记法(TUNEL)检测耳蜗内细胞凋亡情况;半数标本进行耳蜗基底膜铺片观察毛细胞形态及酶学变化。结果顺铂组用药后ABR阈值升高,毛细胞受损,琥珀酸脱氢酶(SDH)活性减弱,有部分毛细胞凋亡,与对照组及川芎嗪组比较差异具有统计学意义(P<0.05)。顺铂加川芎嗪组用药后ABR阈值升高,毛细胞受损较轻,凋亡细胞较少,与顺铂组比较差异有统计学意义(P<0.05)。结论川芎嗪能降低顺铂的耳毒性。

Objective： To explore the protective effect of ligustrazine against cisplatin-induced ototoxicity.Methods： Thirty adult guinea pigs were divided into three groups.Group A received saline as controls.Group B received cisplatin（3 mg/kg） injections for 6 consecutive days.Group C first received ligustrazine（140 mg/kg） for 3 days,and then received both cisplatin（3 mg/kg） and ligustrazine（140 mg/kg） for 6 consecutive days.Both ears of all the animals were tested with auditory brain stem response（ABR） before and on the 10th day of the corresponding treatment.All the animals were sacrificed after the final recording session.Half of the cochleas in each group were collected for the surface preparation of basilar membrane and light microscopy analysis.The apoptosis of hair cells of the other half cochleas were observed by TUNEL method.Results： The ABR threshold was significantly increased in cisplatin group compared to the controls.The damage and apoptosis of hair cells were detected in Group B and Group C.Compared to group C,the ABR threshold of group B were higher,and the damage and apoptosis of hair cells were significantly higher（P0.05）.Conclusion： This study suggests that ligustrazine seems to reduce cisplatin-induced ototoxicity.