中文摘要：

目的研究Smad4基因缺陷小鼠中耳及内耳的病理形态学改变，探讨Smad4基因对中耳及内耳发育的影响。方法利用建立的Smad4基因敲除嵌合体小鼠模型，通过火棉胶包埋HE染色观察Smad4（＋/＋）与Smad4（＋／-）小鼠的情况；通过耳蜗基底膜铺片琥珀酸脱氢酶染色观察Smad4（＋／＋）与Smad4（＋／-）小鼠的耳蜗内、外毛细胞数量；应用扫描电镜观察Smad4（＋／＋）与Smad4（＋／-）小鼠的内耳超微结构。结果火棉胶包埋HE染色显示：Smad4（＋／＋）与Smad4（＋／-）小鼠耳蜗大小、耳蜗转数均未见异常，中耳鼓膜正常，听小骨锤骨、砧骨、镫骨及关节结构正常，骨细胞排列紧密，Smad4（＋／＋）与Smad4（＋／-）之间没有差异。Smad4（＋／＋）小鼠耳蜗Corti器结构完整，未圯异常，血管纹厚薄均匀，血管腔腔径大小均匀。内、外毛细胞及内外柱细胞、支持细胞无异常，螺旋神经节细胞未见缺失；Smad4（＋／-）小鼠耳蜗钩端至-回外毛细胞轮廓不清，呈均质化，细胞核消失。Deiter细胞核下沉或消失，相应的螺旋神经节细胞大量缺失。耳蜗基底膜铺片琥珀酸脱氢酶染色显示：Smad4（＋／-）和Smad4（＋／＋）小鼠均有明显的局限于Corti’S器底同的外毛细胞缺失，其中Smad4（＋／-）小鼠外毛细胞的缺失，比Smad4（＋／＋）小鼠更明显（P〈0．01），两个基因型小鼠的内毛细胞均未见缺失。扫描电镜显示：Smad4（＋／＋）小鼠未见明显病理变化，Smad4（＋／-）小鼠耳蜗钩端外毛细胞静纤毛广泛散在性缺失，外毛细胞的表皮板穿孔、自溶，其周边与指状突小皮板断离。两个基因型小鼠耳蜗内毛细胞纤毛均未见明显改变。结论Smad4基因敲除后内耳形态发生明显改变，表明Smad4基因缺陷导致小鼠内耳细胞损害。

英文摘要：

Objective To explore the influence of the Smad4 gene upon ears by studying pathological changes of Smad4 knockout （mutant） mice. Methods By using celloidin embedded and HE stained sections we observed ears of Smad4 （＋/＋） and Smad4 （＋/-） mice. By way of a basilar membrane surface preparation with fumarie reduetase staining, we carried out inner and outer hair cell counting. By scanning electron microscopy we observed pathological changes of inner ear in Smad4 （＋/＋） and Smad4 （＋/-） mice. Results Through examination of celloidin sections it was showed that there were a normal tympanic membrane, malleus, incus, stapes and articulation in both Smad4 （＋/＋） and Smad4 （＋/-） mice. Smad4 （＋/＋） mice had a normal stria vascularis with a normal blood vessel lumen. Comparing with Smad4 （＋/＋） mice, there was a deficience of outer hair cells and nuclei of Deiters＇ cells from hook to basal turn with a massive deficience of corresponding spiral ganglion cells. Surface preparations showed that there was a significant difference in numbers of hair cell absence between Smad4（＋/＋） and Smad4（＋/-） mice （P 〈 0.01）. There was no absence of inner hair cells in Smad4 （＋/＋） and Smad4 （＋/-） mice. Scanning electron microscopy showed that there was no obvious pathologic changes in Smad4 （＋/＋） mice while there were extensive absence of stereocilia of outer hair cells at hook and perforation or autolysis in the cuticular plate associated with disjunction with the phalangeal prominence in Smad4 （＋/-） mice. Conclusion There are obvious pathologic changes in the inner ear of Smad4 （＋/-） mice, which indicates that mutant Smad4 result in damages of inner ear cells.