顺铂对小鼠耳蜗螺旋神经节细胞凋亡及caspase-3表达的影响

目的:建立小鼠顺铂(CDDP)耳毒性模型,研究不同剂量顺铂对小鼠耳蜗螺旋神经节细胞凋亡及caspase-3表达的影响。方法:采用末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)技术检测螺旋神经节细胞的凋亡;应用免疫组织化学Envision法检测caspase-3在螺旋神经节中的表达;同时结合听脑干反应(ABR)测试,观察用药前后小鼠听力的变化。结果:不同剂量顺铂组小鼠体重和听力明显下降,与对照组比较均有显著性差异(P0.05,P0.01);并且随着顺铂给药剂量的增加,小鼠耳蜗螺旋神经节中TUNEL阳性细胞数增多,以及caspase-3表达明显增强。结论:应用小鼠能建立可靠的顺铂耳毒性模型;顺铂可导致耳蜗螺旋神经节细胞凋亡,而且此凋亡过程中有caspase-3的参与,进一步证实了凋亡可能是顺铂耳毒性机制之一。

Effect of cisplatin on apoptosis of spiral ganglion cell and expression of caspase-3 in mouse cochlea

Objective： To establish a mice model of cisplatin-induced ototoxicity, and to investigate the effect of cisplatin on apoptosis of spiral ganglion cell and expression of caspase-3 in mouse cochlea. Methods： Terminal deoxynucleotidyl transferase-mediated nick end labeling method （TUNEL） was used to monitor the apoptosis of spiral ganglion cell. Envision method of immunohistochemistry was applied to detect the expression of caspase-3 in cochlea. Auditory brainstem response （ABR） was measured to observe the change of hearing. Results： The weight and hearing of mice in different dose of cisplatin groups were declined significantly as compared with those of control group （ P 〈 0.05, P 〈 0.01）, and the TUNEL positive cell number and expression of caspase-3 were greater remarkably with the more cisplatin injected. Conclusion： A mouse model of cisplatin-induced ototoxicity can be established. Cisplatin can lead to the apoptosis of spiral ganglion cells, and caspase-3 has participated in this apoptosis process, which approves further that apoptosis might be one of the mechanisms of cisplatin ototoxicity.