摘要
目的探讨氨基糖苷类抗菌药物对重症肌无力(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的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重症肌无力(EAMG)模型,随机将EAMG小鼠分为MG组、生理盐水(NS)组和氨基糖苷类抗菌药物(庆大霉素,依替米星,阿米卡星)治疗组,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(RNS)检查和血清中乙酰胆碱受体抗体(AchRab)水平的检测。结果成功复制小鼠实验性自身免疫性重症肌无力47只;末次免疫后第7天和注射抗菌药物后第14天庆大霉素组(1.312、2.067)、阿米卡星组(1.111、1889)和依替米星组(1.263、1.632)小鼠的症状评分明显高于MG组(1.000、1.200)(P<0.05);RNS检测阳性率庆大霉素组(2667%、69.23%)、阿米卡星组(22.22%、58.82%)和依替米星组(31.58%、63.16%)明显高于MG组(20.00%、4000%)(P<0.05);各组AchRab滴度明显高于MG组(P<0.01);抗生素治疗后第14天各实验组小鼠神经肌肉接头处AchR的表达明显低于MG组。结论氨基糖苷类抗菌药物可以加重MG症状,其机理可能与促进AchR的免疫原性,提高AchRab滴度,阻滞乙酰胆碱与受体的结合、加重肌肉神经接头处AchR的丢失或破坏运动终板突触前。
OBJECTIVE To study the security of aminoglycosides and the underlying mechanisms of the exacerbation of myasthenia gravis(MG). METHODS Acetylcholine receptor (AchR) protein was extracted from electric organ of Narcine timlei, and C57BL/6 mice were immunized with the extracted protein in complete Freund′s adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG) models. EAMG mice were divided randomly into MG group, normal saline(NS) group and aminoglycosides group. To compare the effects of treatment of aminoglycoside antibiotics, the clinical symptom of mice immunized with AchR in CFA was evaluated 7 days after the last immunostimulation and 14 days after the antibiotics treatment. Repetitive nerve stimulation (RNS) and the levels of acetylcholine receptor antibody (AchRab) were tested at the same time. RESULTS Forty seven cases of EAMG were established successfully. The mean clinical symptom grades of gentamicin group (1.312, 2.067) , amikacin group (1.111, 1.889) and the etimicin group (1.263, 1.632) were higher than MG group (1.000, 1.200) (P<0.05). The positive percentage of RNS of three aminoglycosides groups were 69.23% , 58.82% and 63.16%, respectively, and the percentage of decrement of these mice were higher than MG group (P<0.05). The levels of AchRab and the expression of AchR on neuromuscular junction (NMJ) of experimental mice were also higher than MG group. CONCLUSIONS Aminoglycosides would aggravate the symptom of myasthenia gravis, promoting the immunogenicity of AchR, increasing the level of AchRab in serum related to locking the combination of acetylcholine (Ach) and receptor, exacerbating the loss of AchR on NMJ and destroying the structure of presynaptic and postsynaptic membrane.
出处
《中华医院感染学杂志》
CAS
CSCD
2004年第12期1341-1343,共3页
Chinese Journal of Nosocomiology
基金
华中科技大学同济医学院课题赞助(No:200217)
