Early effect of tacrolimus in improving excitation-contraction coupling in myasthenia gravis
Early effect of tacrolimus in improving excitation-contraction coupling in myasthenia gravis
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DOI：
10.1016/j.clinph.2012.01.017
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发表时间：
2012-09-01
影响因子：
4.7
通讯作者：
Shimohama, Shun
中科院分区：
文献类型：
--
作者：
Imai, Tomihiro;Tsuda, Emiko;Shimohama, Shun
目的：他克莫司(FK506)是一种大环内酯类T细胞免疫调节剂，用于治疗重症肌无力(MG)。据报道，除了免疫抑制外，他克莫司还有可能通过增强兰尼定受体(RyR)功能来增加肌肉力量。然而，在临床研究中，很少有人尝试证明他克莫司作为RyR增强剂的早期效果。方法：对20例MG患者用针电极刺激三叉神经后，同时记录咀嚼肌复合肌肉动作电位(CMAP)和下颌运动相关电位(MRPs)。根据CMAP和MRP的潜伏期差计算兴奋-收缩(E-C)耦合时间(ECCT)。用压敏片测量咬合力。在他克莫司(3 mg/d，1次/d)治疗前和治疗后4周内，对咀嚼肌重复神经刺激(RNS)、ECCT和咬合力进行一系列评估。评估的中位(平均，范围)间隔为2(2.4，1-4)周。结果：他克莫司治疗后咬合力增加，临床症状改善按美国重症肌无力基金会分级，但咬合力差异无统计学意义。Wilcoxon配对符号列检验显示，在他克莫司治疗1-2周后评估的12名患者和3-4周后评估的8名患者中，ECCT显著缩短。相反，他克莫司短期治疗后，咀嚼肌CMAP和%减少量没有明显变化。意义：他克莫司的这种早期作用可能意味着药物上增强了RyR功能，改善了MG患者的E-C偶联。(C)2012年国际临床神经生理学联合会。爱思唯尔爱尔兰有限公司出版。版权所有。
Objectives: Tacrolimus (FK506) is a macrolide T-cell immunomodulator used to treat myasthenia gravis (MG). Besides immunosuppression, tacrolimus has been reported to have the potential to increase muscle strength by enhancing ryanodine receptor (RyR) function. However, few attempts have been made to demonstrate the early effect of tacrolimus as an RyR enhancer in clinical investigation.Methods: In 20 MG patients, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The excitation-contraction (E-C) coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT and bite force were performed before and within 4 weeks of tacrolimus (3 mg day (1)) treatment. The median (mean, range) interval of assessment was 2 (2.4, 1-4) weeks. We also measured serum antibodies against RyR, acetylcholine receptor and muscle-specific receptor tyrosine kinase.Results: Bite force increased after tacrolimus treatment accompanying clinical improvement assessed by Myasthenia Gravis Foundation of America classification, but the bite force difference did not reach statistical significance. Wilcoxon matched-pairs signed-ranks test detected a significant ECCT shortening in 12 patients assessed after 1-2 weeks of tacrolimus treatment as well as in eight patients assessed after 3-4 weeks. In contrast, masseteric CMAP and % decrement showed no significant changes after shortterm tacrolimus treatment.Significance: This early effect of tacrolimus may imply a pharmacological enhancement of RyR function to improve E-C coupling in MG. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.