[目的]探讨抗肌肉特异性激酶(MuSK)多克隆抗体对重症肌无力(MG)的诱导作用.[方法]选择雌性Lewis大鼠,随机分为实验组和对照组,分别腹腔注射给予抗MuSK多克隆抗体和生理盐水.观察大鼠的临床症状,并记录体质量变化.48h后处死大鼠,取肋间肌、胫前肌和腓肠肌进行免疫荧光试验,检测抗MuSK多克隆抗体与细胞膜上MuSK的结合情况,应用透射电子显微镜观察神经肌肉接头处(NMJ)的形态学变化.[结果]两组均未出现明显的肌力下降及活动减少等肌无力症状.免疫荧光试验检测结果显示,实验组肋间肌、胫前肌和腓肠肌的细胞膜表面均可观察到黄绿色荧光,提示抗MuSK多克隆抗体与细胞膜上MuSK发生结合,而对照组未观察到荧光.透射电子显微镜观察结果显示,实验组大鼠NMJ的突触后膜皱褶分级明显减少,皱褶明显短缩变直,突触间隙略变宽,突触后膜相对平坦,符合MG的特征性病理改变.[结论]注射给予实验大鼠抗MuSK多克隆抗体后未能诱导出MG的临床症状,但通过免疫荧光试验和透射电子显微镜可观察到大鼠肌肉组织细胞膜处发生抗MuSK多克隆抗体与MuSK结合现象,且NMJ可观察到MG特征性形态学变化.
OBJECTIVETo study the pathogenicity of muscle specific kinase(MuSK)antibody(MuSKAb)in myasthenia gravis(MG).METHODS Twelve female Lewis rats were randomly divided into experimental and control groups with 6rats in each group.The experimental rats were injected intraperitoneally with MuSK polyclonal antibodies and control rats with normal saline.The clinical symptoms and body weight were recorded until 48 hours after injection.All the rats were executed and the intercostals,pretibial and gastrocnemius muscles were obtained.Then the binding of MuSKAb to MuSK on the cryosections of muscles,and the changes in ultrastructures of neuromuscular junction(NMJ),were observed using immunofluorescence test and transmission electronic microscope,respectively.RESULTSNo obvious clinical symptom,such as myodynamia decline and decreased activity,or change of body weight was observed in both experimental and control rats.The yellow-green fluorescence appeared on the cell membrane in muscle tissues of experimental rats,but did not in control ones,indicating that MuSKAb bound to the antigen MuSK.In addition,the morphological defects(synaptic gutter flattening and a decreased number of slitlike junctional folds),similar to clinical MG,were observed in NMJ of experimental group.CONCLUSIONInjection of MuSK polyclonal antibodies fails to induce clinical symptoms in rats.However,MuSKAb can bind to MuSK on the cell membrane of muscles.Furthermore,there exist morpholygical changes of ultrastructure similar to clinical MG.in NMJ.