5-磷酸二酯酶抑制剂对庆大霉素所致豚鼠耳毒性影响的研究

The Experimental Study on the Effect of the Inhibitor of PDE5 on the Ototoxicity of Gentamicin in Guinea Pigs

梁媛;张淑君;李庆红;黄跃雁;马桂琴;曹静;张洁;刘春丽;袁玉洁;李俊鹏;

1:承德医学院附属医院耳鼻喉科

摘要
目的探讨5-磷酸二酯酶(PDE5)抑制剂对庆大霉素所致豚鼠耳毒性的听功能及耳蜗形态学的影响。方法采用随机数字表法将36只豚鼠分为空白对照组、庆大霉素组和PDE5抑制剂组,每组各12只;其中空白对照组未给予特殊处理,庆大霉素组和PDE5抑制剂组给予连续腹腔注射庆大霉素120 mg·kg(-1)·d(-1)·d(-1)3周后,庆大霉素组继续给予腹腔注射生理盐水4 ml·kg(-1)3周后,庆大霉素组继续给予腹腔注射生理盐水4 ml·kg(-1)·d(-1)·d(-1),PDE5抑制剂组给予腹腔注射他达那非(选择性5-磷酸二酯酶抑制剂)2 mg·kg(-1),PDE5抑制剂组给予腹腔注射他达那非(选择性5-磷酸二酯酶抑制剂)2 mg·kg(-1)·d(-1)·d(-1),均连续给药4周后,分别测试庆大霉素给药前1天、庆大霉素给药后3周、给药生理盐水和他达那非后1、2及4周三组豚鼠听性脑干反应(ABR)阈值及波Ⅰ潜伏期,扫描电镜观察生理盐水和他达那非给药4周后豚鼠耳蜗毛细胞的形态变化。结果在庆大霉素给药3周后,PDE5抑制剂组与庆大霉素组ABR阈值及波Ⅰ潜伏期较空白对照组明显升高及延长(均为P<0.01),PDE5抑制剂组与庆大霉素组之间差异无统计学意义(P>0.05)。在给予他达那非干预1、2、4周时,PDE5抑制剂组ABR阈移及波Ⅰ潜伏期均小于庆大霉素组,差异有统计学意义(均P<0.01)。用药4周后扫描电镜观察,庆大霉素组豚鼠耳蜗外毛细胞听毛紊乱、融合及缺失;而PDE5抑制剂组耳蜗病变较轻,听毛仅有轻微倒伏、融合现象。结论 PDE5抑制剂能够减轻庆大霉素所致豚鼠耳蜗毛细胞损害,对庆大霉素引起的听力损伤有一定的治疗作用。
关键词
庆大霉素;耳毒性;5-磷酸二酯酶;形态学
基金项目(Foundation):
承德市科学技术研究与发展计划项目(201801A048)
作者
梁媛;张淑君;李庆红;黄跃雁;马桂琴;曹静;张洁;刘春丽;袁玉洁;李俊鹏;
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