亚氨乙基赖氨酸拮抗顺铂所致豚鼠耳蜗毒性的实验研究

THE ANTI-TOXIC EFFECT OF IMINOETHYL-LYSINE ON GUINEA PIG'S COCHLEA DAMAGED BY CISPLATIN

目的 探讨亚氨乙基赖氨酸对顺铂所致豚鼠耳蜗毒性的拮抗作用。方法 将豚鼠分为正常对照组 (A组 )、实验对照组 (B组 )、实验组 (C组 )、亚氨乙基赖氨酸组 (D组 ) ,每组 10只。B和C组ip顺铂 10mg·kg-1·d-1,连续 4d ,同时C组ip亚氨乙基赖氨酸 10mg·kg-1·d-1,B组ip等量生理盐水。D组ip亚氨乙基赖氨酸 10mg·kg-1·d-1,腹腔同时注射与B组等量生理盐水。每组豚鼠在实验前后均行听觉脑干反应测听 (ABR)检测听阈。用免疫组织化学方法检测诱生型一氧化氮合成酶 (iNOS)在各组耳蜗的表达 ,同时用扫描电镜观察各组豚鼠耳蜗形态。结果 B组和C组ABR听阈有显著性差异 ,B组豚鼠听功能损伤明显重于C组 (P <0 .0 5 )。iNOS在A、D两组表达呈阴性 ,在B组和C组耳蜗表达呈阳性 ,且在B组的表达明显强于C组。B组耳蜗外毛细胞的损伤明显较C组重。结论 iNOS在顺铂所致豚鼠耳蜗损伤中呈阳性表达。亚氨乙基赖氨酸对iNOS活性有明显抑制作用 ,且能拮抗顺铂豚鼠耳蜗毒性 。

OBJECTIVE To investigate the anti-toxic effect of iminoethyl-lysine on the guinea pig's cochlea damaged by cisplatin. METHODS The experiment consisted of four groups: normal control group (group A), experimental control group (group B), experimental group (group C) and iminoethyl-lysine group (group D).The hearing threshold of guinea pigs of each group were measured with the method of auditory brain response (ABR) before and after experiment. The expression of inducible nitric oxide synthase (iNOS) in the cochlea of each group was detected with the method of immunohistochemistry. And the cochlea structure of each group was examined with scanning electronic microscope. RESULTS There were significant difference in ABR hearing threshold between group B and group C ( P <0.05), the auditory function of group B was much more severely hurt than that of group C. The expression of iNOS in the cochlea of group A and group D were negative, but positive in group B and group C. The expression of iNOS in the cochlea of group B was much stronger than that of group C. The damage of outer hair cells of group B was much more severely hurt than that of group C. CONCLUSION The expression of iNOS is positive in the guinea pig's cochlea damaged by cisplatin. Iminoethyl-lysine can inhibit the activity of iNOS significantly, and also have the anti-toxic effect on cochlea injury induced by cisplatin. It suggests that nitric oxide takes very important part in the process of cochlea injury.