凋亡及其相关蛋白在实验性自身免疫性内耳病的表达

Apoptosis and apoptosis-related proteins in experimental autoimmune inner eardisease

目的:通过一种自身免疫性内耳病的动物模型,了解凋亡与自身免疫性内耳病发病机制的关系,明确凋亡及其相关分子cmyc和Bcl-2在自身免疫性内耳病小鼠耳蜗中的表达,及在其发生发展中的作用。方法:采用内耳抗原、完全弗氏佐剂及百日咳减毒活菌免疫C57BL/6小鼠的动物模型,检测听性脑干反应阈的改变,免疫组织化学法检测耳蜗中cmyc和Bcl-2分子的表达变化。结果:免疫后小鼠听性脑干反应阈显著提高,cmyc和Bcl-2在正常和免疫小鼠耳蜗的神经元细胞均有表达,而Bcl-2在二者的内毛细胞、血管纹和螺旋韧带均无表达。两种分子均可在浸润的炎性细胞表达,表达Bcl-2的炎性细胞数量在病程后期逐渐增多。结论:体液与细胞介导的免疫损伤均参与了自身免疫性内耳病的发生,凋亡和坏死均造成了自身免疫性内耳病耳蜗结构和功能的破坏,凋亡在耳蜗损伤和浸润的炎性细胞消散的过程中起重要作用,Bcl-2对抑制耳蜗中发生的凋亡起重要的作用。

Objective ：To understand the relationship between apoptosis and autoimmune inner ear disease （AIED） through an experimental autoimmune inner ear disease model, and elucidate the expression of apoptosis-related molecules and mechanisms involved in pathogenesis of AIED in the inner ear. Methods ：The AIED model were given a subcutaneous injection with inner ear antigens （IEAg） ,complete freund adjuvant （CFA） and diluted solution pertussis. Auditory brainstem response（ABR） and the expression change of cmyc and Bcl-2 in cochlea were detected. Results： The ABR thresholds from IEAg sensitized animals were elevated significantly. Cmyc and Bcl-2 can be detected in neuron cell but Bcl 2 positive cells were not detectable in inner hair cells,stria vaseularis and spiral ligament both in normal and AIED mice. Two kinds of molecules were detectable on some of infiltrated inflammatory cells ,Bcl-2 positive infiltrated cells were increased in number at the late stage of AIED. Conclusion：Both cell and humoral-mediated immune injury cause the AIED. Apoptosis and necrossis may be involved in destruction of cochlear structure as well as its function,apoptosis may play an important role both in inducing damage to the cochlear and inducing resolution of inflammation in AIED. Bcl-2 also plays a crucial role in suppression of the process of apoptosis in cochlea of AIED mice.