CBA/CaJ和C57BL/6J小鼠全耳蜗毛细胞随着年龄增长不同损害模式的比较

Comparison of different damage patterns of cochlear hair cells between CBA/CaJ and C57BL/6J mice with aging

目的探讨和比较CBA/CaJ与C57BL/6J小鼠全耳蜗毛细胞随着年龄增长不同损害模式与规律。方法选择年龄在6个月、12个月、18个月和24个月的CBA/CaJ和C57BL/6J小鼠各32只,其中每个年龄各8只,全身麻醉下取耳蜗,进行全耳蜗基底膜铺片,将全耳蜗内、外毛细胞计数结果输入计算机并应用耳蜗图软件,按照对应的不同年龄进行两个鼠种耳蜗毛细胞密度对比和统计学分析。结果CBA/CaJ小鼠于12月龄耳蜗顶部外毛细胞开始出现轻度损失,伴随着年龄增加,外毛细胞损失继续扩大,以顶部向中部发展为主,后期内毛细胞也出现损失。从18月龄开始,耳蜗外毛细胞损失与上个年龄组比较均增加显著(P<0.05)。而C57BL/6J小鼠于6月龄耳蜗底部均已出现外、内毛细胞损失,而且以外毛细胞损失为主,此后伴随着年龄增加,毛细胞损失不断扩大,于6月龄开始,耳蜗外、内毛细胞损失与同龄CBA/CaJ小鼠比较均明显增加(P<0.05),12月龄开始与同鼠种上个年龄组比较均明显增加(P<0.05)。结论CBA/CaJ小鼠耳蜗毛细胞损害遵循着从顶部和底部两端开始,向中部延伸,但顶部毛细胞损害比底部严重的病变规律。C57BL/6J小鼠耳蜗毛细胞损害遵循着主要从耳蜗底部开始,逐渐向中部和顶部扩展的病变规律。外毛细胞损害比内毛细胞早。C57BL/6J小鼠毛细胞损害比CBA/CaJ小鼠早。提示两个鼠种均可作为老年性毛细胞凋亡研究动物模型,但以C57BL/6J小鼠模型更适合短期观察研究,两者间所出现的毛细胞变化差别可能与Cdh23基因是否变异和缺失有关。

Objective To investigate the different patterns of cochlear hair cell loss in CBA/CaJ and C57 BL/6 J mice with aging.Methods Thirty-two CBA/CaJ or C57 BL/6 J mice at 6,12,18,and 24 months of age were selected,with 8 mice in each age group.The cochleae were removed under general anesthesia,and then the intact basement membrane was taken out from the cochlea and used for making glass slides of whole cochlear basement membrane.The numbers of cochlear inner and outer hair cells were counted,and input into the computer using cochleogram software.The density of cochlear hair cells in the two mouse strains were compared at corresponding ages,and statistically analyzed.Results The outer hair cells from cochlear apex in the CBA/CaJ mice at 12 months of age began to loss slightly.With the increase of age,the losses of outer hair cells were continuously expanded,and their developments were mainly from the top to the middle part.The losses of inner hair cells also occurred in the later period.From 18 months of age on,the losses of the cochlear outer hair cells were increased significantly by comparison with that of the last age(P<0.05).However,the losses of the outer and inner hair cells at the cochlear bottom appeared in C57 BL/6 J mice at the 6 months of age,and the losses were mainly of the outer hair cells.From then on,the losses of outer hair cells were continuously expanded with the increase of age.From 6 months of age on,the losses of the cochlear outer and inner hair cells were increased significantly compared with that of the CBA/CaJ mice at the same age(P<0.05).From 12 months of age on,the losses of the cochlear outer and inner hair cells were increased significantly compared with that of the same strain(P<0.05).Conclusions The damages of cochlear hair cells in the CBA/CaJ mice obey the rule of pathological changes that began at both ends of the cochlear top and bottom,and extended to the middle part,but the damages of hair cells at cochlear top were more serious than that at the cochlear bottom.The damages of cochlear hair cells in the C57 BL/6 J mice obey the rule of pathological changes that began mainly at the cochlear bottom and gradually extended to the middle and top.The damages of outer hair cells are earlier than that of inner hair cells.The damages of hair cells in C57 BL/6 J mice are earlier than that in CBA/CaJ mice.These result suggest that both species of mice can be used as animal models for the research of age-related hair cell apoptosis,but the model of C57 BL/6 J mouse is more suitable for the research of short-term observation.The differences of hair cell changes between the CBA/CaJ and the C57 BL/6 J mice may be related to the mutation and deletion of Cdh23 gene.