周围神经脱髓鞘豚鼠模型听神经病变及听功能研究

目的:通过建立实验性变态反应性神经炎这一周围神经脱髓鞘动物模型,观察其听神经病变,初步探讨其听性脑干反应(ABR)和听神经复合动作电位(CAP)的改变。方法:以粗提的牛外周神经髓鞘碱性蛋白(MBP)作为抗原,免疫实验组豚鼠;对照组以生理盐水代替MBP。检测动物血清抗MBPIgG水平、坐骨神经传导速度,观察坐骨神经、听神经病理改变;检测ABR、CAP阈值及潜伏期;观察内耳病理损伤。结果:实验组血清抗MBPIgG水平升高,与对照组相比P<0.01;实验组坐骨神经传导速度减慢,与对照组相比P<0.05;透射电镜发现坐骨神经、听神经脱髓鞘改变;免疫前后实验组14只(26耳)出现ABR反应阈升高,伴Ⅰ、Ⅲ、Ⅴ波潜伏期明显延长,与对照组比较P<0.01,而Ⅰ～Ⅲ、Ⅲ～Ⅴ波间期与对照组比较P>0.05;CAPN1、N1波潜伏期延长,与对照组比较P<0.01;另有4只(8耳)仅出现潜伏期延长而无阈值升高;免疫组织化学显示内耳免疫损伤部位主要在蜗神经、内耳神经纤维、螺旋神经节;扫描电镜显示内毛细胞纤毛紊乱、胞质溢出。结论:实验性变态反应性神经炎动物模型作为一种可靠的周围神经脱髓鞘动物模型,其病变可累及听神经出现听神经脱髓鞘改变,ABR和CAP阈值升高、潜伏期明显延长,该模型可望成为探讨听神经脱髓鞘的听力学表现的一种有用的动物模型。

Alteration of the auditory function and auditory nerve pathology in Guinea pigs with peripheral nerve demyelination

OBJECTIVE: To study the auditory function and auditory nerve pathological changes of the experimental allergic neuritis (EAN) animal model in Guinea pigs. METHOD: To establish the animal model of EAN, heterologous myelin basic protein (MBP) of peripheral nerve was used to the immunize Guinea pigs. Serum anti-MBP-IgG levels, sciatic nerve conduction velocity (NCV), hearing thresholds and wave latencies, and pathological changes in auditory nerve, sciatic nerve and cochlea were observed. The immune lesions in inner ear were examined with immunohistochemistry. Auditory brainstem response (ABR) and compound action potential (CAP) were assayed weekly before and after immunization for a period of seven weeks. In the control group, antigen was replaced by the 0.9% saline. RESULT: Serum anti-MBP-IgG levels increased significantly in experimental group comparing with the control group (P < 0.01). Seiatic nerve conduction velocity decreased after immunization, as comparing with the control group (P < 0.01). Sciatic nerve and auditory nerve showed the existence of demyelination. There was significant increase of ABR and CAP thresholds and the latencies of wave I, III, V and N1 in experimental group when compared to the controls (P < 0.01), but no significant changes in inter-peak latencies of I-III, III-V were found( P > 0.05). In addition, there were 4 Guinea pigs (8 ears) in which only appeared lengthened wave latencies with normal hearing thresholds. Immunohistochemistry indicated that antibodies to inner ear from the MBP-sensitized animals distributed in cochlear nerve, neurofiber of inner ear and spiral ganglion cells. Cochlear scanning electron microscopy showed the pathology of inner hair cell with stereociliary disorder and cytoplasmic protrusions. CONCLUSION: The results suggest that auditory nerve demyelination are involved in this experimental allergic neuritis animal model and sciatic nerve demyelination as well, and the auditory abnormalities are elicited. This animal model seems to be a promising one of auditory dysfunction due to demyelination disorders.