摘要
目的 :探讨线粒体DNA缺失的组织器官间差异及其与老化和老年性耳聋的关系。方法 :依月龄将大鼠分为青年、中年和老年组 ;测试ABR阈值后从其不同器官组织和外周血中提取DNA ;PCR检测线粒体DNA4 83 4缺失 ,定量分析 ;克隆、测序。结果 :①随年龄增加 ,大鼠的ABR平均阈值明显升高 ;②所有老年大鼠的耳蜗、蜗核、大脑、心肌 (1例除外 )、肝脏和肌肉组织中均存在mtDNA4 83 4缺失 ,外周血仅少数缺失 ;③中青年组线粒体DNA4 83 4缺失的发生率和缺失占总mtDNA的百分比均低于老年组 (P <0 0 1) ;④mtDNA4 83 4缺失存在明显的器官组织间差异 ,肝脏组织中缺失占总mtDNA的百分比最高。结论 :大鼠多种器官组织中mtDNA4 83 4缺失随增龄而增加 ,而且存在器官组织间差异 ,检测外周血白细胞的mtDNA缺失并不能反映体内各器官组织中mtDNA缺失的发生情况 ,与听觉有关的耳蜗、蜗核组织中mtDNA缺失与老年聋的发生有关。
Objective:To determine if there is a different mitochondrial DNA (mtDNA) deletion level in different wistar rat tissues, and if the mtDNA is involved in the aging and the development of presbycusis. Methods:Wistar rats from 3 age groups were used. All animals were tested for auditory sensitivity using the auditory brainstem response (ABR). The cochlea, cochlear nucleus, brain, heart, liver, temporal muscle and blood were harvested and the total DNA was extracted. The presence of mtDNA 4834 deletions, corresponding to mtDNA 4977 deletions in human, was examined using polymerase chain reaction (PCR), and the mtDNA 4834 deletions were quantitated.Results: ①The results showed a progressive reduction in auditory sensitivity with aging.②The mtDNA 4834 deletion was detected in an age-related manner in all tissues screened except blood.③There was a significant increase in the presence of the mtDNA 4834 deletions in the aged subjects compared with the young subjects (P<0.01).④Quantitative measure showed the mtDNA 4834 deletion level is an age-related manner in all tissues and different tissues have different deletion level. The mtDNA 4834 deletion was found to be at its highest level in the liver, followed by the brain of old animals. Conclusions:These findings indicated that the mtDNA deletion is associated with presbycusis, as well as with aging, and the mtDNA deletion is heterogeneous.
出处
《军医进修学院学报》
CAS
2002年第4期305-307,共3页
Academic Journal of Pla Postgraduate Medical School
基金
国家杰出青年科研基金项目 ( 3972 5 0 2 6 )
