甲磺酸去铁胺抗庆大霉素耳毒性作用及机理研究

目的探讨铁螯合剂甲磺酸去铁胺（ｄｅｆｅｒｏｘａｍｉｎｅｍｅｓｙｌａｔｅ，ＤＦＯ）对抗庆大霉素（ｇｅｎｔａｍｉｃｉｎ，ＧＭ）耳毒性作用及其机理。方法豚鼠随机分为ＧＭ组（１７只）、ＤＦＯ组（８只）、ＧＭ＋ＤＦＯ组（１７只）及对照组（８只），采用听性脑干反应（ａｃｏｕｓｔｉｃｂｒａｉｎｓｔｅｍｒｅｓｐｏｎｓｅ，ＡＢＲ）、耳蜗铺片及透射电镜技术，观察用药前后听反应阈及形态学变化，检测血清尿素氮、肌苷以及ＧＭ浓度，同时测定耳蜗和肾皮质组织中丙二醛、超氧化物歧化酶和铁离子含量。结果ＧＭ组８ｋＨｚＡＢＲ阈移为４０～６０ｄＢ；ＧＭ＋ＤＦＯ组阈移为１５～２５ｄＢ，差异有显著性（Ｐ＜０．０５）。形态学改变与听力变化一致。ＤＦＯ对ＧＭ血药浓度没有影响。ＧＭ组肾功明显损伤，但肾皮质丙二醛、超氧化物歧化酶和铁离子变化差异无显著性（Ｐ＞０．０５），ＧＭ＋ＤＦＯ组耳蜗组织丙二醛和铁离子含量较ＧＭ组明显减少（Ｐ＜０．０５），超氧化物歧化酶含量明显高于ＧＭ组（Ｐ＜０．０５）。结论自由基和铁离子在ＧＭ的耳毒性中起重要作用，ＤＦＯ能有效减轻ＧＭ的耳毒性作用，可能成为有希望的预防药物。

Deferoxamine protects against gentamicin ototoxicity

Objective To study the prevention of gentamicin(GM) ototoxicity by deferoxamine(DFO) in the guinea pig. Methods Guinea pigs were randomly assigned to three experimental groups (GMtreated alone, DFOtreated alone, GM and DFO in combination) and one control group. Acoustic brainstem response (ABR), the surface preparation and transmission electron microscopy were utilized to evaluate the hearing thresholds and the cochlear morphology. To explore the mechanism associated with deferoxamine protection, serum levels of GM, BUN and Cr, together with concentration of MDA, SOD and iron in cochlear and renal tissues were measured. Results The GM group developed up to 40 60 dB of the threshold shifts at 8 kHz while the GM DFO group developed only 15 25 dB of the threshold shifts (P<0.05). Morphological changes were consistent with functional changes. DFO did not alter serum levels of GM. Renal function of GM group was damaged obviously. However, changes of MDA, SOD and iron were not significant (P>0.05). MDA and iron concentrations in cochlear tissue of the GM DFO group were significantly lower than those in the GM group (P<0.05) while SOD level was much higher than that in GM group. Conclusion This study suggests that free radical and iron involve in GM ototoxicity and DFO may become a promising therapeutic agent that can be used to reduce gentamicin ototoxicity.