CAJ | 학술논문

目的观察缝隙连接蛋白30（connexin，Cx30）基因敲除纯合子Cx30（-/-）小鼠（P3、P7、P10、P30、P60、P90）耳蜗血管纹（stria vascularis，SV）超微结构的发育情况，进一步探讨GJB6基因突变导致耳聋的机制。方法选取Cx30（-/-）小鼠P3、P7、P10、P30、P60、P90等6个发育阶段的小鼠，用透射电镜观察耳蜗血管纹超微结构变化情况。结果P3～P90耳蜗血管纹边缘细胞、中间细胞、基底细胞呈现一个由不成熟至成熟的正常发育过程，至P90时均未发现退化性表现或缺失改变。血管纹毛细血管随着小鼠日龄的增加，管腔逐渐变宽，逐渐成熟，高倍镜下见P3、P7、P10时血管内皮细胞结构无明显异常，P30时内皮细胞之间的纤维突起出现疏松，P60时内皮细胞之间出现较大的裂隙，P90时这种改变更加严重，内皮细胞之间出现扩大的细胞间隙。结论 GJB6基因缺陷本身并不影响耳蜗组织血管纹的形态发育和成熟，GJB6缺失引起小鼠出生后逐渐出现的血管纹内皮细胞超微结构的改变导致内皮细胞屏障破坏，可能引起耳蜗内电位缺失，从而造成听力的下降。
목적관찰봉극련접단백30（connexin，Cx30）기인고제순합자Cx30（-/-）소서（P3、P7、P10、P30、P60、P90）이와혈관문（stria vascularis，SV）초미결구적발육정황，진일보탐토GJB6기인돌변도치이롱적궤제。방법선취Cx30（-/-）소서P3、P7、P10、P30、P60、P90등6개발육계단적소서，용투사전경관찰이와혈관문초미결구변화정황。결과P3～P90이와혈관문변연세포、중간세포、기저세포정현일개유불성숙지성숙적정상발육과정，지P90시균미발현퇴화성표현혹결실개변。혈관문모세혈관수착소서일령적증가，관강축점변관，축점성숙，고배경하견P3、P7、P10시혈관내피세포결구무명현이상，P30시내피세포지간적섬유돌기출현소송，P60시내피세포지간출현교대적렬극，P90시저충개변경가엄중，내피세포지간출현확대적세포간극。결론 GJB6기인결함본신병불영향이와조직혈관문적형태발육화성숙，GJB6결실인기소서출생후축점출현적혈관문내피세포초미결구적개변도치내피세포병장파배，가능인기이와내전위결실，종이조성은력적하강。
Objective To observe the ultrastructure of the stria vascularis(SV) of cochlear duct in connexin 30 knockout mice Cx30 (-/-) and to further explore the pathogenesis of deafness caused by GJB6 mutation. Methods Cx30 (-/-) homozygous mice at six time points after birth (P3, P7, P10, P30, P60, P90) were selected. The cochleae were dissected and observed under transmission electron microscope. Results The marginal cell, intermediate cell and basal cells of the SV developed normally from P3 to P90 in Cx30 (-/-) mice. No obvious cell degeneration or loss was found up to P90. The cavity of SV capillary became broader over time. The endothelium cells showed no obvious difference as compared with those of wild-type mice at postnatal ages P3, P7 and P10 under high-power lens. But at P30 intercellular connection between endothelium was loose and a gap occurred at P60. This change became more and more obvious and the enlarged intercellular spaces were found between these cells at P90. Conclusion GJB6 mutation may not hinder the development of marginal cell, intermediate cell and basal cells of the SV in cochlea. However, the changes of ultrastructure of SV endothelium may induce the damage of endothelial cell barrier and lead to the endocochlear potential and hearing loss.