重症肌无力中枢神经系统受损模型

目的近年研究结果表明，重症肌无力（ＭＧ）病变部位并不仅仅局限于神经肌接头（ＮＭＪ）处突触后膜烟碱型乙酰胆碱受体（ｎＡＣｈＲ），烟碱型乙酰胆碱受体抗体（ＡＣｈＲ－ａｂ）病理作用可能波及到中枢神经系统（ＣＮＳ）。因此，有必要建立模拟ＭＧ患者ＣＮＳ损害的动物模型，研究ＭＧ患者脑脊液中存在的ＡＣｈＲ－ａｂ引起ＣＮＳ损害的机制。方法从ＭＧ患者血中提取的ＡＣｈＲ－ａｂ经侧脑室穿刺注入到大鼠脑室系统，然后观察其症状和体征，以及用脑干听觉诱发电位仪（ＢＡＥＰ）检测鼠脑干听觉传导中枢功能。用免疫组化法（ＡＢＣ）研究ＡＣｈＲ－ａｂ与ＣＮＳ神经－ｎＡＣｈＲ之间免疫结合反应及其分布。结果大鼠除了出现脑干听觉传导中枢功能障碍外，还出现类似于ＭＧ动物模型表现的症状。免疫组化研究结果显示，神经－ｎＡＣｈＲ样阳性免疫反应广泛分布于ＣＮＳ许多部位。结论脑室内注入的ＡＣｈＲ－ａｂ与神经－ＡＣｈＲ结合引起ＣＮＳ功能障碍和出现ＭＧ动物模型样症状。我们首次建立的中枢受损的ＭＧ模型将有助于阐明ＡＣｈＲ－ａｂ引起中枢受损和ＣＮＳ下位运动神经元引起横纹肌收缩无力的机制。

A novel model of central nervous system involvement in myasthenia gravis

Objective A number of reports have suggested that the pathological role of anti acetylcholine receptor antibody (AChR ab) presented in myasthenia gravis (MG) plasma is not only limited on the postsynaptic acetylcholine receptor (AChR) at the neuromuscular junction, but also may spread to the central nervous system (CNS). The purpose of this study was to establish a model that mimics CNS dysfunction in MG patients to investigate the action of AChR ab existed in MG patients cerebral spinal fluid on the CNS function. Methods The effects of AChR ab on the CNS function and central auditory pathway were investigated with the brainstem auditory evoked potential (BAEP) examination and observing the rats' symptoms, before and after injection of AChR ab into the lateral ventricular system. Immunohistochemical method was used to study the immune reaction between AChR ab and central neuronal nicotinic AChR and its distribution in the rats CNS. Results The BAEP examination revealed dysfunction of the rats central auditory pathway. Besides, the rats also manifested the experimental autoimmune MG (EAMG) symptoms. Immunohistochemical study demonstrated neuronal nicotinic AChR like immunoreactivity distributed all over the CNS. Conclusion Cross reactivity of AChR ab from MG and neuronal nicotinic AChR from rats' brain led to develop in the rats CNS dysfunction and EAMG symptoms. The novel MG model provided strong evidence of CNS involvement in MG and might help with further investigation to clarify the mechanism of AChR ab in causing the CNS dysfunction as well as in generating muscle weakness.