不同种类抗生素影响重症肌无力小鼠神经肌肉接头处的传递功能

背景临床工作发现多种抗生素可影响甚至加重重症肌无力已存在的神经肌肉接头处传递功能的障碍,使患者的肌无力症状恶化.目前,国内外在重症肌无力动物模型上进行抗生素对神经肌肉接头处传递功能影响的报道较少.随着新型抗生素的出现,有必要进一步探讨各类抗生素对神经肌肉接头处传递功能的影响.目的探讨头孢菌素类、喹诺酮类和氨基糖甙类抗生素对重症肌无力神经肌肉接头处传递功能的影响,为临床安全、合理选用抗生素治疗重症肌无力提供实验依据.设计以实验动物为研究对象,随机对照试验.单位一所大学医院的感染科、神经内科和药剂科.材料实验于2002-03/2003-01在华中科技大学同济医学院神经科学研究所完成.健康、雌性C57BL/6小鼠150只,随机分为正常组10只;重症肌无力组10只;生理盐水组10只;抗生素治疗组120只.抗生素治疗组分为庆大霉素组、依米替星组、环丙沙星组、氟罗沙星组、头孢呋新组和头孢他啶组,每组20只.干预以丁氏双鳍电鳐的电器官的乙酰胆碱受体免疫3次建成EA重症肌无力模型.生理盐水组、各抗生素治疗组于末次免疫后第7天开始按10 mg/kg体质量分别注射生理盐水和抗生素,连续注射14 d;重症肌无力组和正常组不做任何处理.分别于末次免疫后第7天和抗生素治疗后第14天进行症状评分、低频重复电刺激检查和血清中乙酰胆碱受体抗体水平的检测.主要观察指标①肌无力症状评分.②低频重复电刺激的衰减率.③血清乙酰胆碱受体抗体的水平.结果注射抗生素后第14天庆大霉素组、依米替星组、环丙沙星组和氟罗沙星组小鼠的平均症状评分明显高于重症肌无力组,头孢呋新组和头孢他啶组小鼠的平均症状评分与重症肌无力组无明显差别;低频重复电刺激检测衰减幅度庆大霉素组(21.22±4.63)%、依米替星组(19.08±4.25)%、环丙沙星组(22.25±4.95)%和氟罗沙星组(21.71±4.99)%明显高于重症肌无力组(15.75±2.22)%,头孢呋新组(15.25±2.87)%和头孢他啶组(15.25±3.30)%与重症肌无力组无明显差别;乙酰胆碱受体抗体水平庆大霉素组、依米替星组、环丙沙星组和氟罗沙星组明显高于重症肌无力组,头孢呋新组和头孢他啶组与重症肌无力组无明显差别.结论氨基糖甙类和喹诺酮类抗生素可以加重重症肌无力小鼠业已存在的神经肌肉接头处传递功能的障碍,而头孢菌素类抗生素没有明显的影响.

Effect of different kinds of antibiotics on transmission function at neuromuscular junction in mice with myasthenia gravis

BACKGROUND: It is recently found that some kinds of antibiotics can aggravate the obstruction of neuromuscular junction(NM J) transmission,exacerbate myasthenia gravis (MG). Hitherto, there are few reports about the effect of antibiotics on transitive function on animal models. Along with the appearance of new antibiotics, the effects of the antibiotics on NMJ transitive function need to be further observed.OBJECTIVE: To investigate the effect of aminoglycoside antibiotics, fluoroquinolone antibiotics and cephalosporin antibiotics on the transitive function of NMJ in MG, and to provide an experimental basis for using those antibiotics securely in clinic and for selecting those antibiotics to treat MG properly.DESIGN: Randomized controlled study based on experimental animals.SETTING: Department of nosocomial infection, neurology and pharmacy in a university hospital.MATERIALS: The experiment was conducted at the Neurological Institute of Tongji Medical College, Huazhong University of Science and Technology from March 2002 to January 2003. Totally 150 healthy female C57BL/6mice, 6 - 8 weeks old, weighting 18 - 20 g, were divided randomly into 4groups: normal group( n = 10), MG group( n = 10), saline group( n = 10)and antibiotics group( n = 120) . Mice in antibiotics group were divided randomly again into gentamicin group, etimicin group, ciprofloxacin group,fleroxacin group, cefuroxime group and cephradine group, with 20 mice in each group.INTERVENTIONS: C57BL/6 mice were immunized with the acetylcholine receptor(AChR) protein in complete Fruend' s adjuvant(CFA) to establish experimental autoimmune myasthenia gravis(EAMG) . Mice in saline group were injected normal saline and mice in antibiotics group were injected antibiotics(10 mg/kg), lasted 14 days. Mice in MG group were without any treatments. On the 7th day after the last immunization and the 14th day after the antibiotics treatments, MG scores was evaluated, repetitive nerve stimulation(RNS) and the levels of acetylcholine receptor antibody(AChRab)were tested at the same time.RESULTS; The mean symptom scores on the 14th day after the antibiotics treatment with gentamicin, etimicin, ciprofloxacin and fleroxacin were higher than that in MG group, and there was no significant difference in the mean symptom scores among cefuroxime group, cephradine group and MG group. The decrement percent of RNS in gentamicin group (21.22 ± 4.63)% ], etimicin group (19.08 ±4. 25)% ], ciprofloxacin group (22.25 ±4.95)% ] and fleroxacin group (21.71 ±4.99)% ] were higher than that in MG group(15.75 ±2.22)% ], but no difference was found in the attenuation rate among cefuroxime group(15.25 ±2. 87)% ],cephradine group ( 15.25 ± 3.30)% ] and MG group. The levels of AChRab in gentamicin, etimicin, ciprofloxacin and fleroxacin groups were also higher than that in MG group, but no difference was found among cefuroxime group, cephradine group and MG group.CONCLUSOIN: Aminoglycoside and fluoroquinolone antibiotics can aggravate the obstruction of NMJ transmission, and cephalosporin antibiotics have no obvious effect on the obstruction of NMJ transmission function in MG.