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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。
Objectives Recent studies have shown that myasthenia gravis (MG) lesions are not limited to the postsynaptic nicotinic acetylcholine receptor (nAChR), nicotinic acetylcholine receptor antibody (AChR- ab) Pathological effects may affect the central nervous system (CNS). Therefore, it is necessary to establish an animal model to simulate CNS damage in MG patients and to study the mechanism of CNS damage caused by AChR-ab existing in cerebrospinal fluid of MG patients. Methods AChR-ab extracted from the blood of patients with MG was injected into the ventricular system of rats through lateral ventricle puncture. Then the symptoms and signs of AChR-ab were observed. The brainstem auditory central nervous system function was detected by brainstem auditory evoked potentials (BAEP). Immunohistochemistry (ABC) was used to investigate the immunoreactivity and distribution of AChR-ab with CNS neuro-nAChR. Results In addition to the dysfunction of auditory brainstem auditory-brainstem center, rats also showed symptoms similar to that of animal model of MG. Immunohistochemical results showed that neuronal-nAChR-like immunoreactivity was widely distributed in many parts of the CNS. Conclusions Intraventricular injection of AChR-ab and neuro-AChR cause CNS dysfunction and MG-like animal model-like symptoms. Our first established central lesioned MG model will help elucidate the mechanism by which AChR-ab causes central impairment and weakening of the striated muscle caused by CNS motor neurons.