苏木醇提取物对自身免疫性重症肌无力小鼠淋巴细胞功能影响的实验研究

目的采用中药苏木醇提取物治疗实验性自身免疫性重症肌无力(EAMG)小鼠,观察其T淋巴细胞和B淋巴细胞功能的变化情况,探讨苏木治疗重症肌无力的作用机制。方法80只昆明小鼠被随机分为EAMG治疗组(20只)、EAMG对照组(20只)、佐剂对照组(20只)和正常对照组(20只)。采用乙酰胆碱受体(AChR)加完全福氏佐剂(CFA)的方法多次免疫小鼠,复制实验性自身免疫性重症肌无力小鼠模型;佐剂对照组模型制备成功后仅予完全福氏佐剂。所有小鼠均于末次免疫后7～14d行游泳试验和肌电图检查,进行模型鉴定。EAMG治疗组小鼠于末次免疫后第15天起,每天胃内灌注苏木醇提取物0.2ml/只,EAMG对照组、佐剂对照组及正常对照组胃内灌注等量生理盐水,连续给予4周后处死小鼠,应用MTT比色法检测T淋巴细胞和B淋巴细胞转化功能。结果(1)EAMG对照组小鼠的T淋巴细胞吸光度差值为(0.257±0.025),较佐剂对照组(0.147±0.022)及正常对照组(0.154±0.017)明显增高(P<0.01);EAMG治疗组小鼠的吸光度差值为(0.174±0.040),较EAMG对照组明显降低(P<0.01),但仍高于佐剂对照组和正常对照组(P<0.05);佐剂对照组与正常对照组相比,差异无显著性意义(P>0.05)。(2)EAMG对照组小鼠的B淋巴细胞吸光度差值(0.789±0.101)较佐剂对照组(0.502±0.125)及正常对照组(0.493±0.09)明显增高(P<0.01);EAMG治疗组小鼠的吸光度差值为(0.590±0.120),较EAMG对照组明显降低(P<0.01),但仍高于佐剂对照组及正常对照组(P<0.05);佐剂对照组与正常对照组间相比,差异无显著性意义(P>0.05)。结论苏木具有下调实验性自身免疫性重症肌无力小鼠淋巴细胞功能,抑制N2乙酰胆碱受体抗原诱导特异性免疫反应。     

苏木醇提取物对实验性自身免疫性重症肌无力小鼠腓肠肌组织结构的影响

目的观察中药苏木醇提取物治疗实验性自身免疫性重症肌无力(EAMG)小鼠的临床疗效,探讨其对EAMG小鼠腓肠肌组织结构的影响。方法 80只昆明小鼠被随机分为EAMG治疗组、EAMG对照组、佐剂对照组和健康对照组4组。EAMG治疗组和EAMG对照组采用乙酰胆碱受体(AChR)加等量完全福氏佐剂(CFA)两次免疫小鼠制作EAMG模型,佐剂对照组以等量CFA于相同时间进行免疫;EAMG治疗组于末次免疫后第15天起,每天按0.2 mL/只胃内注入苏木醇提取物治疗,EAMG对照组、佐剂对照组和健康对照组予等量生理盐水。于治疗30 d后分别取各组腓肠肌组织行醋酸铀及枸椽酸铅双重染色观察腓肠肌组织细胞形态学变化。结果治疗后第30天健康对照组和佐剂对照组电镜下腓肠肌病理表现相似,腓肠肌细胞核形状不规则,核内染色质分布均匀;肌丝排列整齐,其间有丰富的形态正常结构完整的线粒体、糖原等,肌膜完整。EAMG对照组可见线粒体肿胀变形,线粒体嵴断裂、溶解,甚至形成空白区,肌原纤维排列紊乱、断裂,部分肌原纤维溶解。EAMG治疗组小鼠线粒体形态尚可,偶有线粒体肿胀,线粒体外膜缺损.肌原纤维排列基本整齐,肌丝变细,部分地方有肌丝断裂征象,未见线粒体和肌丝溶解征象,与EAMG对照组有明显差别。结论苏木醇提取物能明显改善EAMG小鼠腓肠肌超微结构,可能是治疗MG的有效药物。     

设计耐受原并用鼻黏膜耐受治疗EAMG的方法学研究

目的　设计特异性耐受原 ,通过其鼻黏膜耐受治疗对实验性自身免疫性重症肌无力 (EAMG)发病过程的影响 ,以探讨该疗法在模型应用中的可行性。方法　用 Lewis大鼠建立 EAMG模型 ,选取双类似物作为耐受原在致敏同时给予鼻黏膜耐受治疗 ,动态观察大鼠体重及临床评分改变。结果　虽然治疗组大鼠发病率不降低 ,但是在 EAMG急性期和慢性期 ,其临床症状均较对照组减轻 (P <0 .0 5 )。结论　用双类似物鼻黏膜耐受可以达到治疗 EAMG的目的 ,其结果为抗原特异性治疗重症肌无力 (MG)和其他自身免疫性疾病 (AID)提供了依据。     

实验性自身免疫性重症肌无力模型大鼠腓肠肌低密度脂蛋白受体相关蛋白4表达的特点

目的探讨实验性自身免疫性重症肌无力(EAMG)模型大鼠腓肠肌低密度脂蛋白受体相关蛋白4(LRP4)表达的特点。方法将30只大鼠随机分为EAMG组、对照组和空白组。以小鼠乙酰胆碱受体(AChR)基因为模板合成AChR抗原,以Lewis大鼠为免疫动物。EAMG组采取主动免疫法将AChR抗原与弗氏佐剂混合制成乳剂,注射入大鼠背部皮下。对照组在相同部位注射等量的弗氏佐剂。空白组在相同部位注射等量的生理盐水。8周后使用低频重复电刺激(RNS)检测肌电RNS衰减率。采用蛋白免疫印迹法检测腓肠肌LRP4含量。结果 EAMG组所有大鼠在8周后出现肌无力症状,对照组、空白组大鼠无肌无力症状。EAMG组大鼠RNS衰减率明显高于对照组和空白组(均P0.05)。EAMG组大鼠腓肠肌LRP4蛋白的相对含量明显低于对照组和空白组(均P0.05)。结论 EAMG大鼠中,当AChR被自身抗体破坏时,可能导致包含LRP4在内的整条信号通路受损,进而使LRP4含量减少。LRP4是神经肌肉接头信号通路完整的重要分子。     

重症肌无力被动转移动物模型的研究

目的 :探讨血清阳性 (SPMG)和阴性重症肌无力 (SNMG)被动转移动物模型 (P EAMG)的异同。方法 :用ELISA法将重症肌无力 (MG)患者分为SNMG和SPMG两组 ,然后分别用两组患者血清制作P EAMG ,观察两组小鼠的临床表现、电生理及神经肌接头(NMJ)的改变。结果 :SPMG和SNMG组小鼠均表现出明显的肌无力症状 ,低频重复电刺激出现明显衰减反应 ,但SNMG组小鼠肌无力症状较SPMG组明显为轻 ,SPMG和SNMG组小鼠NMJ处棕黄色沉积物明显减少、变细短。结论 :SNMG和SPMG均是自身抗体介导的自身免疫性疾病 ,但两者不完全相同     

实验性自身免疫性重症肌无力大鼠CD28/CTLA-4:B7表达水平的研究

目的探讨实验性自身免疫性重症肌无力(EAMG)大鼠外周血单个核细胞(PBMC)CD28/CTLA4B7的表达水平。方法健康、雌性Lewis大鼠24只,随机分为正常组、EAMG组、完全福(氏)佐剂(CFA)对照组。EAMG组大鼠分别于足垫、腹部及背部皮下多点注射丁(氏)双鳍电鳐电器官乙酰胆碱受体蛋白乳剂1mL,第4周再次注射上述乳剂免疫大鼠。CFA对照组只接受等量的CFA皮下注射。初次免疫后7周分离PBMC,应用RTPCR和流式细胞术分析方法,分别进行CD28、CTLA4mRNA及B71、B72蛋白表达水平检测。结果(1)正常组大鼠PBMCCD28、CTLA4mRNA表达水平较低,尤其CTLA4mRNA仅有极少量表达;前二者在EAMG组大鼠表达水平均明显增加(P<0001),而正常组和CFA对照组之间表达水平差异无显著性(P>005)。(2)正常大鼠B71、B72在PBMC上仅少量表达而EAMG组表达明显增加(P<0001),正常组与CFA对照组比较差异均无显著性(P>005)。结论EAMG大鼠存在PBMCCD28/CTLA4B7协同刺激分子的表达异常,CD28/CTLA4B7共刺激通路可能参与了机体异常免疫反应的诱导与维持,在重症肌无力(MG)的发生过程中发挥重要作用。     

苏木醇提物对重症肌无力患者干扰素-γ水平的影响

目的观察苏木醇提物治疗重症肌无力(MG)患者的乙酰胆碱受体抗体(AChRab)、干扰素-γ(IFN-γ)水平变化,探讨苏木醇提物治疗MG可能的免疫机制。方法采用ELISA法对苏木治疗组和常规治疗组MG患者治疗前、后及30例正常对照组外周血AChRab、IFN-γ水平进行检测并作分析。结果①苏木治疗组与常规治疗组MG患者血清ACh-Rab水平治疗前后均较正常对照组显著升高(P<0.05),苏木治疗组与常规治疗组MG患者治疗前血清AChRab水平比较差异无显著性意义(P>0.05),而治疗后差异有显著性意义(P<0.05);②苏木治疗组与常规治疗组MG患者血清IFN-γ水平治疗前后均较正常对照组显著升高(P<0.05),苏木治疗组与常规治疗组MG患者治疗前血清IFN-γ水平比较差异无显著性意义(P>0.05),治疗后差异有显著性意义(P<0.05)。结论苏木醇提物可能通过降低IFN-γ水平从而减少血中AChRab的生成,缓解肌无力症状。     

双类似物鼻黏膜耐受在EAMG发病中的预防作用机制

目的　采用双类似物 (Lys2 62 -Ala2 0 7)对实验性自身免疫性重症肌无力 (EAMG)模型进行鼻黏膜耐受不同时间点预防性给药 ,观察临床及免疫指标变化 ,以探讨其对 EAMG免疫发病中的预防作用机制。方法　应用乙酰胆碱受体 (ACh R)加福 (氏 )佐剂致敏 Lewis大鼠建立 EAMG模型 ,在致敏前 1 0 d(预防耐受 A组 )及致敏当日 (预防耐受 B组 )经鼻腔给药 ,评价给药后 A、B组及对照组大鼠体重、临床症状 ,观察肌电图变化、检测致敏第 42天血清抗 ACh R抗体 Ig G及其亚型含量和第 5 0天处死后淋巴结单个核细胞 (MNC)中 IFN-γ、IL-4及 IL-1 0分泌细胞含量变化。结果　 (1 )急性期和慢性期 A、B组体重增加而临床症状明显轻于对照组 ,慢性期 A组临床症状轻于 B组 ;(2 ) A、B组低频重复电刺激出现明显衰减的阳性率低于对照组 ;(3 )慢性期 A、B组 Ig G含量明显低于对照组 ,且 A组低于 B组 ,各组间抗体亚型 Ig G1含量无明显差异 ,而 A、B组的 Ig G2 a和 Ig G2 b含量明显少于各自对照组 ,B组 Ig G2 b含量高于 A组 ;(4 ) A、B组淋巴结中的 IFN-γ、IL-4及 IL-1 0阳性细胞含量均明显低于各自对照组。结论　Lys2 62 -Ala2 0 7鼻黏膜预防耐受不仅可有效地抑制临床症状 ,并使致病性最强的ACh R特异性 Ig G2抗体分泌量减少 ,Ig G     

阿托伐他汀诱导BMDCs源性外泌体对EAMG模型大鼠临床症状的缓解及与自然杀伤细胞和自然杀伤T细胞的关系

目的 分析阿托伐他汀诱导骨髓来源树突状细胞(BMDCs)源性外泌体对实验性自身免疫性重症肌无力(EAMG)模型大鼠临床症状的缓解及与自然杀伤细胞和自然杀伤T细胞的关系。方法 分别采用二甲基亚砜、阿托伐他汀与BMDCs进行共培养,分别设置对照组(二甲基亚砜与BMDCs共培养)和实验组(阿托伐他汀与BMDCs共培养),通过流式细胞术检测2组BMDCs表面共刺激分子的表达水平; 通过梯度离心法提取2组BMDCs源性外泌体,将其注射于EAMG大鼠体内,实验组给予阿托伐他汀,对照组未进行任何治疗,记录2组大鼠临床症状评分; 采用流式细胞术测定2组大鼠淋巴结单个核细胞中自然杀伤细胞和自然杀伤T细胞的比例。结果 实验组BMDCs表面共刺激分子CD80和CD86表达水平较对照组显著下降(P<0.01),而2组主要组织相容性复合体Ⅱ(MHC-Ⅱ)分子表达水平无明显差异(P>0.05); 实验组免疫2、4、6周后临床症状评分较对照组均明显降低(P<0.01)。与对照组比较,实验组大鼠淋巴结单个核细胞中自然杀伤细胞的比例明显升高(P<0.01),而2组大鼠淋巴结单个核细胞中自然杀伤T细胞的比例无明显差异(P>0.05)。结论 阿托伐他汀诱导BMDCs分泌源性外泌体可有效减轻EAMG大鼠临床症状,其作用机制可能与提高大鼠淋巴结单个核细胞中自然杀伤细胞的比例有相关     

大剂量糖皮质激素冲击治疗重症肌无力80例临床分析

目的观察大剂量糖皮质激素冲击治疗重症肌无力的临床效果。方法将80例重症肌无力患者随机分为对照组和观察组,分别采用小剂量递增与大剂量冲击治疗,比较2组治疗效果、重症肌无力改善情况及治疗过程中不良反应发生情况。结果观察组疗效良好率显著高于对照组,观察组治疗后肌无力评分显著低于对照组,2组并发症发生率差异无统计学意义(P0.05)。结论大剂量糖皮质激素冲击治疗重症肌无力临床效果显著,不良反应发生率低,值得临床推广应用。     

Experimental myasthenia gravis induced in mice by passive transfer of human myasthenic immunoglobulin : Evidence for an ameliorating effect by alpha-fetoprotein

The induction of experimental autoimmune myasthenia gravis (EAMG) was studied by the passive transfer of gamma-globulin from myasthenia gravis (MG) patients to C57BL/6 mice. Muscular weakness and electromyographic decrements (EMG) could be consistently induced in all mice injected with gamma-globulin from certain selected MG patients. There was, however, no correlation between the antiacetylcholine receptor antibody titre in the donor gamma-globulin and the ability to induce EAMG. The possible beneficial effects of immunoregulatory alpha-fetoprotein (AFP) treatment were investigated employing the passive EAMG model. Mice were protected against the onset of severe symptoms provided the AFP was administered before and after passive transfer. The exaggerated fatigue characteristics associated with murine EAMG as detected by EMG could be alleviated by AFP treatment. These findings raise the possibility that AFP may be of some therapeutic value in the control of MG.     

Effects of sex hormones on experimental autoimmune myasthenia gravis.

To examine whether exacerbation of myasthenia gravis (MG) can be induced by changes in sex hormone levels we immunized 20 female Lewis rats with torpedo antigen to induce experimental autoimmune MG (EAMG). Ten of the animals underwent surgical ovariectomy prior to the induction of EAMG and 10 served as controls. Anti-acetylcholine receptor antibody (AChR-ab) titres and the degree of decrement on repetitive stimulation electromyography (REMG) at 3 Hz were obtained at base line and compared between rats with and without ovariectomy and a second control group of naïve rats. Three rats in each group were then injected with excess oestrogen and progesterone for one week, and three of the remaining rats in each group were given sham injections, and the degree of decrement on REMG and AchR-ab titres were re-evaluated. Immune reactivity of peripheral lymphocytes and splenic lymphocytes from all groups and controls was also determined. A comparable number of animals with and without ovariectomy developed clinical and electromyographic EAMG. The extent of decrement on REMG and AChR-ab titres did not change following hormonal replacement. Lymphocyte reactivity was similar for rats with and without ovariectomy. In conclusion, sex hormones do not appear to have an influence on the susceptibility to and the severity of MG.     

Acetylcholine release in diaphragm of rats with chronic experimental autoimmune myasthenia gravis.

Recent evidence indicates that in chronic experimental autoimmune myasthenia gravis (EAMG) and in human myasthenia gravis, the defect of neuromuscular transmission results from immune-mediated destruction of post-synaptic membrane at the neuromuscular junction, with a reduction in the density of acetylcholine (ACh) receptors and decreased sensitivity to ACh released by nerve impulses. In the present study, the amount of ACh released by nerve impulse in rats with chronic EAMG and control rats of the same age, weight, and sex was compared. Phrenic nerve-hemidiaphragm preparations were stimulated in vitro, and the amount of ACh released was measured by bioassay. Despite a marked reduction in the amplitude of miniature end-plate potentials in chronic EAMG, ACh output at rest and during stimulation was not different from that of control rats. These data support the concept that the defect of neuromuscular transmission is due to a reduction of postsynaptic sensitivity to ACh.     

Facilitatory effects of 4-aminopyridine on neuromuscular transmission in disease states

The in vitro effects of 4-aminopyridine (4-AP) on neuromuscular transmission were determined by microelectrode techniques in intercostal muscles from patients with myasthenia gravis (MG) and the Eaton-Lambert syndrome (ELS), and in forelimb muscles from rats with experimental autoimmune myasthenia gravis (EAMG). In MG and EAMG, the amplitudes of miniature endplate potentials (MEPPs) and endplate potentials (EPPs) were reduced, and there was increased sensitivity to the blocking action of d-tubocurarine (dTc). In ELS, MEPP amplitude was normal but the average number of acetylcholine quanta released by nerve impulses was reduced, causing subthreshold EPPs. In EAMG muscle, 4-AP produced dose-dependent increases in EPP amplitude and in the duration of indirectly elicited muscle action potentials but no changes in MEPP amplitude and resting membrane potential. 4-AP completely reversed the postsynaptic blockade produced by dTc and EAMG. 4-AP appears to facilitate neuromuscular transmission in EAMG, MG, and ELS by increasing the neurally evoked transmitter release, thus overcoming either the pre- or the postsynaptic neuromuscular blockade.     

激发型CD40单克隆抗体对实验性自身免疫性重症肌无力耐受的影响

目的 探讨激发型CD40单克隆抗体(CD40mAb)对未成熟树突状细胞(iDC)诱导实验性自身免疫性重症肌无力(EAMG)耐受的影响. 方法 20只Lewis大鼠按照随机数字表法分为正常组、EAMG对照组、耐受组和CD40mAb组,每组5只.耐受组和CD40mAb组每只大鼠于背部皮下分4点分别注射总量为1 mL的乙酰胆碱受体(AChR)+iDC,其中CD40mAb组每只大鼠在接种iDC的同时和次日分别给予CD40mAb腹腔注射,0.5mg/次.EAMG对照组注射1 mL无血清培养基.正常组不做任何处理.3周后用AChR和完全弗氏佐剂(CFA)免疫,观察免疫7周后重症肌无力(MG)相关指标的改变. 结果 耐受组大鼠和正常组大鼠一样,用AChR和CFA免疫后,MG相关指标无明显改变;而CD40mAb组大鼠和EAMG对照组一样,产生了明显的MG症状,重复电刺激出现明显衰减,血清AChRab滴度明显增高,神经肌肉接头呈现典型的MG样改变. 结论 激发型CD40mAb可阻止AChR负载的iDC诱导EAMG耐受,提示iDC功能异常可能与MG异常免疫反应的启动密切相关.

Abstract：

Objective To investigate the effect of agonist CD40 monoclonal antibody (CD40mAb) on the tolerance of experimental autoimmune myasthenia gravis (EAMG) induced by immature dendritic cells (iDCs). Methods Lewis rats were equally randomized into normal group,EAMG group, tolerance group and CD40mAb treatment group (n=5). Rats in the tolerance group and CD40mAb treatment group were vaccinated with AChR pulsed iDCs; and rats in the CD40mAb treatment group were intraperitoneally injected CD40mAb at a dosage of 0.5 mg once when performing the vaccination and on the 2rd d of vaccination. One mL serum-free medium was given to the rats in the EAMG group; normal group did not receive any treatment. Three weeks after that, rats in the above 4 groups were immunized with AChR and complete Freund's adjuvant (CFA). Seven weeks after the immunization, the corresponding indexes of MG were observed: behavioral assessment was performed and electromyogram was employed to detect the repetitive nerve stimulation on these rats; enzyme-linked immunosorbent assay (ELISA) was used to determine the level of AChRab; the pathological changes of neuromuscular junction were also detected. Results Just as the rats in the normal group, the rats in the tolerance group did not have significant changes in any of the corresponding indexes of MG after being immunized with AChR and CFA. In contrast, rats in both EAMG group and CD40mAb treatment group showed typical changes in the corresponding indexes of MG: their electromyogram wave amplitude obviously attenuated; the level of serum AChRab increased and neuromuscular junction appeared as a typical damage of MG. Conclusion Agonist CD40mAb could abrogate the tolerance of EAMG induced by AChR pulsed iDCs, suggesting that the dysfunction of DCs is related to the priming of abnormal immune of MG.     

Interleukin 10 aggravates experimental autoimmune myasthenia gravis through inducing Th2 and B cell responses to AChR

The damage of acetylcholine receptor (AChR) at neuromuscular junctions of experimental autoimmune myasthenia gravis (EAMG), an animal model of human MG, is mediated by B cells which require T cell help. The Th2 associated cytokine IL-10 suppresses production of cytokines released by Th1 cells and is considered for treatment of human autoimmune diseases. To evaluate the role of IL-10 in EAMG, rhIL-10 was administered daily to Lewis rats by the subcutaneous route starting at the day of immunization and continued for 7 weeks. IL-10 failed to abrogate EAMG at low dose (0.1 or 1 microg/day) and at the dose of 3 microg/day caused earlier onset and aggravated clinical signs of EAMG when compared to EAMG rats injected with PBS only. Although Th1 responses reflected by AChR-induced lymphocyte proliferation and levels of IFN-gamma secreting cells, as well as AChR-induced Th1 cytokine mRNA expression was suppressed, augmented IL-4 mRNA expression and AChR-specific B cell responses may play an important role in the failure of IL-10 to abrogate EAMG. This study implicates a critical precaution in planning immunotherapy of IL-10 in antibody-mediated autoimmune diseases, e.g. MG.     

NGF对AChRAb脑内注射所致中枢神经损害的保护作用

目的　探讨神经生长因子 (NGF)对乙酰胆碱受体抗体 (ACh RAb)脑内注射所致重症肌无力 (MG)大鼠中枢神经系统 (CNS)损害神经细胞凋亡的影响。方法　分别从 MG患者和健康者血中提取 Ig G,注入大鼠脑室系统。以原位末端标记法 (TUNEL)检测脑细胞凋亡情况及动态变化。另一组在注入 ACh RAb后予以 NGF并观察结果。结果　 MG组脑阳性细胞于注 ACh RAb后第 2周出现 ,脑内多部位均有凋亡细胞且逐渐增多 ,以皮层和海马区较明显。NGF组凋亡细胞数少于 MG组 (P <0 .0 5 )。结论　脑室注入 MG患者 ACh RAb可引起大鼠CNS功能障碍 ,神经细胞发生凋亡 ,细胞凋亡在 MG脑损害中可能起重要作用。 NGF能减轻凋亡程度 ,补充NGF可能有助于防治 MG CNS损害。     

乙酰胆碱受体诱导实验性自身免疫性重症肌无力模型的建立

目的采用纯化乙酰胆碱受体(acetylcholine receptors,AChR)免疫大鼠和小鼠以建立实验性自身免疫性重症肌无力(experimental autoimmune myasthenia gravis,EAMG)动物模型。方法以亲和层析法从电鳐电器官提取和纯化AChR,并用其免疫接种Lewis大鼠和C57BL/6小鼠,观察接种动物的临床症状、电生理变化以及AChR抗体产生的情况。结果动物模型临床肌无力症状、翻转悬挂时间(小鼠,P<0.05)、重复神经电刺激(repetitive nerve stimulation,RNS)动作电位衰减率、抗体吸光度(P<0.05)及新斯的明试验均为阳性或有统计学意义。结论纯化电器官AChR作为免疫原,成功诱导产生EAMG动物模型。Lewis大鼠和C57BL/6小鼠均对AChR免疫易感而产生EAMG表现,7~8周龄的C57BL/6更易诱导出类似人类MG表现的EAMG。     

Gabapentin may be hazardous in myasthenia gravis

A patient with painful neuropathy developed ocular, facial, and masticatory weakness and fatigue after 3 months of gabapentin (GBP) treatment (400 mg/day). An elevated level of serum acetylcholine receptor antibodies (AChR-Ab) was detected. The patient recovered following pyridostigmine therapy and withdrawal of GBP and, 2 years later, is practically asymptomatic despite positive AChR-Ab. Because of this clinical observation, we gave 150 mg/kg GBP to rats with experimental autoimmune myasthenia gravis (EAMG). Repetitive nerve stimulation at 3-Hz was performed, and the 5th/1st amplitude ratio was used to calculate the decremental response. In all EAMG rats, GBP induced a transient, abnormal decrement (7-20%) 90 to 240 min after administration. No decrement was induced by GBP in normal rats. Thus, GBP aggravates the decrement in EAMG. The mechanism involved in the hitherto unreported possible unmasking of myasthenia gravis (MG) by GBP is unknown. Gabapentin should be used with caution in this disease.