Effect of different kinds of antibiotics on transmission function at neuromuscular junction in mice with myasthenia gravis / 中国组织工程研究

ABSTRACT

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.