脑室内注射乙酰胆碱受体抗体IgG对大鼠神经元凋亡及一氧化氮合酶表达的影响

目的研究乙酰胆碱受体抗体(AchRab)对大鼠脑内神经元的损害及一氧化氮合酶(NOS)在损害中所起的作用，探讨重症肌无力(MG)中枢神经系统损害的机制。方法将AchRab IgG或健康人的IgG注入大鼠侧脑室。HE染色、TUNEL法检测细胞凋亡；免疫组化方法观察大鼠皮质、海马及杏仁核神经元型一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)表达变化。结果2周后实验组皮质、海马及杏仁核凋亡细胞明显增多，对照组仅见少量凋亡。实验组皮质、海马及杏仁核nNOS神经元数目明显减少。实验组及对照组脑内细胞均来见iNOS表达。结论AchRab脑内注射可诱导神经元凋亡；损伤皮质。海马及杏仁核nNOS神经元；但未能诱导脑内细胞iNOS表达。神经元凋亡损害参与了AchRab对中枢神经损害的机制；nNOS神经元的减少，可能与MG认知功能障碍有密切关系；而神经元的损伤可能与NO的毒性作用无关。

Effects of intraventricular injection of AchRab on the neuronal apoptosis and the expression of nitric oxide synthase in rat brains

Objective To study the damage of neuron and the expression of nitric oxide synthase caused by AchRab IgG and to investigate the pathogenesis of central nervous dysfunction in MG. Methods AchRab IgG or lgG of healthy persons were injected to the lateral ventricle of rats respectively for 4 consecutive days,apoptosis of the neurons was determined with HE and TUNEL staining. Expression of neuronal NOS (nNOS) and inducible NOS(iNOS) was tested by immunohistochemistry. Results Two weeks after the injection,comparing with control groups neuronal apoptosis in cortex,hippocampus and amygdaloid nucleus significantly increased in experimental groups,and nNOS positive neurons in cortex,hippocampus and amygdaloid nucleus significantly reduced. No expression of iNOS was discovered in both groups. Conclusion The results indicate that intraventricular injection of AchRab can induce the neuronal apoptosis,and injury nNOS neurons in the rat brains,but it can not induce the expression of iNOS,which suggestes that neuronal apoptosis may play a role in pathogenesis of AchRab causing CNS dysfunction in MG,but no relation with neurotoxin of nitric oxide. And the loss of nNOS neurons may have close relationship with cognitive dysfunction in MG.