重症肌无力乙酰胆碱受体抗体对大鼠神经元烟碱型乙酰胆碱受体作用

EFFECT OF ACETYLCHOLINE RECEPTOR ANTIBODY DERIVED FROM MYASTHENIA GRAVIS ON THE RAT CENTRAL NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR

为了阐明重症肌无力（ＭＧ）患者中枢神经系统（ＣＮＳ）受损机制，本研究利用免疫组化和脑干听觉诱发电位仪观察了从ＭＧ患者血中提取的乙酰１胆碱受体抗体（ＡＣｈＲａｂ）与神经元烟碱型乙酰胆碱受体（神经－ｎＡＣｈＲ）之间的免疫结合反应及其对大鼠脑干听觉传递中枢功能的影响。结果：首次表明神经－ｎＡＣｈＲ样阳性免疫结合反应弥散地分布于大鼠ＣＮＳ许多部位，如大鼠大脑皮层、脑干各颅神经运动核团、听神经核、脊髓前角运动元和小脑皮层等。注入脑室系统的ＡＣｈＲａｂ除了引起大鼠脑干听觉传递中枢功能障碍外，还引起ＭＧ动物模型样症状。提示：ＡＣｈＲａｂ可与ＣＮＳ中的神经－ｎＡＣｈＲ免疫交叉结合；ＡＣｈＲａｂ的病理作用不仅仅局限于神经肌接头处肌－ｎＡＣｈＲ，还可波及到ＣＮＳ中的神经－ｎＡＣｈＲ。

Immunoreaction between acetylcholine receptor antibody (AChRab) derived from myasthenia gravis (MG) and neuronal nicotinic acetylcholine receptor (AChR) and the action of AChRab on rat brain stem auditory transmission were investigated by immunocytochemistry and brain stem auditory evoked potential (BAEP) in a search for abnormalities indicating central nervous system (CNS) involvement in this disorder. 25μl of AChRab were injected into the ventricular system of rats once every 48 hours for periods of up to a week BAEP examination was taken before and after injection of AChRab. Immunocytochemical investigation of the rat brain sections provided evidence that the neuronal nicotinic AChR like immunoreactivity is widely distributed throughout the rat CNS such as cerebral cortex, hippocampus, motor neurons in brain stem, auditory nucleus cerebellar cortex, etc. Analysis of the immunocytochemical results showed that the distribution property of AChRab in rat CNS correlated well with known neuronal nicotinic AChR subtypes e.g, alpha 7 and alpha 4. BAEP inter peak latency was significantly prolonged in rats after injection of AChRab as compared with the control rats and the rats prior to injection of AChRab. The results indicated that cerebroventricular administration of AChRab not only cause dysfunction of brain stem auditory transmission but also leads to development of experimental autoimmune MG symptoms. It is concluded that AChRab influences the rat brain stem auditory transmission and it is suggested that the pathogenic effect of AChRab is not only limited at neuromuscular junction, but also involves the central neuronal nicotinic AChR.