一氧化氮合酶抑制剂对大鼠耳蜗诱生型一氧化氮合酶mRNA表达的影响

Influence of nitric oxide synthase inhibitor on inducible nitric oxide synthase mRNA expression in rat cochlea

目的观察一氧化氮合酶(NO synthase,NOS)抑制剂L-NAME(N-nitro-arginine methylester)对大鼠耳蜗新霉素诱导的NOS mRNA表达的影响。方法将50只SD(Sprague-Dawley)大鼠分为3组:A组10只,肌肉注射注射用水2mL,1次/d,共14d;B组20只,肌肉注射新霉素,150mg/kg体质量,1次/d,共14d;C组20只,腹腔注射L-NAME,50mg/kg体质量,30min后肌肉注射新霉素,150mg/kg体质量,1次/d,,共14d。应用实时荧光定量逆转录-聚合酶链反应(real time reverse transcription-polymerase chain reaction,real-time RTPCR)技术检测各组耳蜗顶圈、中圈、底圈诱生型NOS mRNA的表达,比较与A组相比,B组和C组诱生型NOS增高比例。结果B组和C组顶圈诱生型NOS的表达增高比例分别为57.10±13.74和40.54±10.99,中圈分别为63.48±12.20和18.45±1.99,底圈分别为71.97±13.15和48.03±11.97,差异均有统计学意义(P<0.05)。结论NOS抑制剂可以抑制新霉素诱导的耳蜗组织NOS mRNA的高表达,减轻此类抗生素的耳毒性。

Objective To investigate the influence of NOS inhibitor L-NAME on neomycin induced NOS mRNA expression in the rat cochlea. Methods Fifty rats were divided into three groups （n = 10 in group A ;n = 20 in group B and C respectively）. The subjects received an intramuscular administration of 2 mL aqua pro injection in group A, 150 mg/kg neomycin in group B and an intraperitoneal injection of L-NAME（50 mg/kg） followed by intramuscular injection of neomycin （150 mg/kg） in group C. All drugs were given once a day for 14 days consecutively. Real-time reverse transcription-poly- merase chain reaction was used to detect the expression of inducible NOS（iNOS） mRNA in apical, middle and basal turn of rat cochleas of each group. The ratios for the iNOS expression of group B and C to group ＇A were compared. Results The iNOS expression ratio for group C to A in the apical, middle and basal turn （57.10 ± 13.74,63.48 ± 12. 20,71.97 ± 13.15） was signifcantly higher than that for group B to A （40.54 ± 10.99,18.45 ± 1.99,48.03 ± 11.97） （P 〈0.05）. Conclusions The NOS inhibitor provides protection against neomycin ototoxicity possibly by inhibiting the iNOS mRNA expression in the cochlea.