喹诺酮类抗生素致重症肌无力加重的反应机制

目的:探讨喹诺酮类抗生素对重症肌无力(MG)治疗的安全性及其引起肌无力加重反应的可能机制。 方法:以丁氏双鳍电鳐电器官的乙酰胆碱受体(AchR)提取蛋白主动免疫C57BL/6小鼠建立实验性自身免疫性 MG(EAMG)模型,随机将EAMG小鼠分为未处理组(A组),生理盐水组(B组)和喹诺酮类抗生素组(C组),分别 于末次免疫后第7天和注射抗生素后第14天进行低频重复电刺激(RNS)检查和血清中AchR抗体(AchRab)水平 的检测。结果:成功复制EAMG小鼠44只;注射抗生素后第14天RNS衰减率和AchRab滴度,C组明显高于A 组(P<0.05及P<0.01)。结论:喹诺酮类抗生素加重MG症状的机理可能与药物提高血清AchRab水平,增加肌 无力评分和肌肉电活动的衰减,从而加重MG神经肌肉接头间传递功能的障碍有关。

Mechanism of Fluoroquinolone Antibiotics Induced Exacerbation in Mice Model of Myasthenia Gravis

Objective: To study the security of fluoroquinolone antibiotics and those underlying mechanisms of the exacerbation of myasthenia gravis (MG) following them. Methods: Acetylcholine receptor (AchR) protein was extracted from electric organ of Narcine timilei, and C57BL/6 mice were immunized with the extracted protein in complete Freund's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into non-treatment group(A group), normal saline group(B group) and fluoroquinolone antibiotics group(C group). Repetitive nerve stimulation (RNS) and the levels of acetylcholine receptor antibody (AchRab) were measured 7 days after the last immuno-stimulation and 14 days after the antibiotics treatment. Results: Forty-four rat models of EAMG were successfully established. Fourteen days after the antibiotics treatment, the decremental rate of RNS and levels of serum AchRab in the C group were higher than in the A group (P<0.05 and P<0.01). Conclusion: Fluoroquinolone antibiotics can aggravate the symptom of MG in related with the increased level of serum AchRab, the elevated decremental rate of neuromuscular junction and then exacerbated blockade.