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目的 观察重症肌无力(myastheniagravis,MG)患者IgG(AchRab)对大鼠脑内一氧化氮合酶(NOS)表达的影响,探讨NOS在MG中造成中枢神经系统损害的机制。方法 将AchRabIgG或健康人的IgG注入大鼠侧脑室,1次/d,连续4次。免疫组化方法观察不同时间点大鼠脑皮质、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)的表达变化。结果 侧脑室注射后1周实验组大鼠皮质、海马神经元nNOS表达量明显减少,后2周实验组皮质、海马神经元nNOS表达下降更为明显,同时杏仁核神经元nNOS表达量也减少;实验组及对照组脑内细胞均未见iNOS表达。结论 AchRab侧脑室内注射可引起大鼠皮质、海马及杏仁核神经元nNOS表达量减少,且2周内这种减少效应随时间延长而增强,但未能诱导脑内细胞iNOS表达,提示AchRab尚可通过抑制大鼠中枢神经系统nNOS表达,降低脑内正常的一氧化氮浓度,减弱一氧化氮对脑组织的保护作用,增加神经元的易损性。
Objective To investigate the effect of IgG (AchRab) on the expression of nitric oxide synthase (NOS) in the brain of myasthenia gravis (MG) patients and to explore the mechanism of NOS damage in the central nervous system of MG. Methods AchRabIgG or healthy human IgG was injected into lateral ventricle of rats, once a day for 4 times. Immunohistochemistry was used to observe the changes of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in cerebral cortex, hippocampus and amygdala in different time points. Results The expression of nNOS in cortex and hippocampus neurons decreased significantly in experimental group 1 week after intracerebroventricular injection, while the expression of nNOS in cortex and hippocampus neurons decreased more obviously in experimental group 2 weeks later, meanwhile the expression of nNOS in amygdala neuron decreased. No iNOS expression was observed in the experimental group and the control group. Conclusion AchRab intracerebroventricular injection can induce the decrease of nNOS expression in the cortex, hippocampus and amygdala of rats, and this decrease effect increases with time but can not induce iNOS expression in brain, suggesting that AchRab By inhibiting the expression of nNOS in the central nervous system of rats, decreasing the normal concentration of nitric oxide in the brain, decreasing the protective effect of nitric oxide on brain tissue and increasing the vulnerability of neurons.