小鼠耳蜗血管纹Na-K-2Cl联合转运子1在顺铂耳毒性发生时的改变

The Alteration Expression of Na-K-2Cl Co-transporter in the Cochlea Stria Vascularis of Mice with Cisplatin

目的研究顺铂(cis-dichlorodiammine platinum,Cisplatin)耳毒性发生后耳蜗血管纹Na-K-2Cl联合转运子1(NKCC1)的表达情况,并初步探讨其机制。方法选取健康CBA/CaJ小鼠20只,随机分为对照组和实验组各10只,实验组动物连续腹腔注射顺铂3.5mg.kg-1.d-1,建立顺铂耳毒性小鼠模型,对照组注射等量生理盐水。以听性脑干反应(ABR)阈值作为评价听功能的指标,检测给药前后小鼠听功能的改变,并采用免疫组织化学(SP法)结合免疫荧光实验技术,观察对照组和实验组小鼠腹腔注射顺铂前后耳蜗血管纹NKCC1表达的变化。结果NKCC1在小鼠耳蜗血管纹主要表达于边缘细胞,而顺铂作用后血管纹边缘细胞的NKCC1表达明显减弱,图像分析显示两组平均灰度值差异有显著统计学意义(P<0.01)。结论小鼠顺铂耳毒性作用后血管纹边缘细胞NKCC1的表达量明显减弱,这可能是顺铂耳毒性发生机制中的一个重要环节。

Objective To investigate the expression of NKCC1 in stria vascularis of the cochlea of mice injected with cisplatin and to determine effects and significance in cisplatin induced ototoxicity. Methods To create the cisplatin- induced deafness model in mice, ABR responses was obtained before and after cisplatin administration. The expression of NKCC1 in stria vascularis of mice and its change after cisplatin exposure were identified by immunohistochemistry as well as immunofluorescence technique. Results Strong expression of NKCC1 protein was found on the basolateral membrane of marginal cells of the stria vascularis, the expression of NKCC1 was reduced at the position after intraperitoned injection of cisplatin. In cisplatin group, the mean gray values of cellular NKCC1 positive reaction products in stria vascularis were lower than those in normal control group （ P 〈 0.01 ）. Conclusion Cisplatin significantly inhibits the expression of NKCC1 of the stria vascularis, sequentially inhibits the activity of NKCC1. The NKCC1 may play an important role in normal cochlea function and K^＋ recycle in inner ear of mice.