大鼠高胆固醇血症与听觉器官线粒体DNA^(4834)缺失的关系

Rat hearing loss and hearing organs mitochondrial DNA^(4834) deletions associated with hypercholesteremia

目的 探讨大鼠高胆固醇血症对听觉器官线粒体DNA483 4 缺失以及听力下降的影响。方法 6 0只大鼠分为实验组 (38只 )和对照组 (2 2只 ) ,实验组大鼠以高胆固醇饲料喂养 ,时间为 6个月 ,建立高胆固醇血症大鼠模型 ;对照组则在相同条件下以普通饲料喂养。通过听性脑干电反应(auditorybrainstemresponses,ABR)检查实验前后ABR阈上升程度。取左侧耳蜗 (实验组 2 1个 ,对照组10个 )和左侧蜗神经核 (实验组 2 7个 ,对照组 13个 ) ,提取DNA ,通过套式聚合酶链反应 (nestpolymerasechainreaction ,nestPCR)扩增检测听觉器官线粒体DNA483 4 (mitochondrialDNA ,mtDNA483 4 )缺失 ,比较两组动物的ABR阈上升程度和听觉器官的mtDNA483 4 缺失率并进行统计分析。结果 ①高胆固醇饲料喂养可造成实验组大鼠血清胆固醇水平明显升高 (t检验 ,P <0 0 5 ) ;②两组大鼠随年龄增加ABR阈均上升 ,高胆固醇血症大鼠的ABR阈上升更加明显 ,和对照组的差异具有显著性 (t检验 ,P<0 0 5 ) ;③所有标本都扩增到正常mtDNA编码tRNA和NADH基因 ,实验组听觉器官mtDNA483 4 缺失发生率较对照组明显增高 ,其差异具有显著性 (χ2 检验 ,P <0 0 5 )。结论 长期高胆固醇血症可以加剧大鼠的听力下降 ,听觉器官mtDNA483 4

Objective To determine whether or not the rat hypercholesteremia contributes to hearing organs mtDNA 4834 deletion and involves in the development of hearing loss Methods The rat hypercholesteremia model ( n =38) was established by feeding with high cholesterol diet and the control group ( n =22) with common diet for 6 months The rats were tested for auditory sensitivity using auditory brainstem response (ABR) Twenty one left cochleae and 27 left cochlear nuclei from experimental group and 10 left cochleae and 13 left cochlear nuclei from control group were harvested The total DNA of them was extracted mtDNA was amplified by nest PCR to examine the presence of mtDNA 4834 deletion Results Our result showed: (1) There is a significant increase in serum cholesterol level and ABR threshold in the experimental group (2) The mitochondrially encoded tRNA and ND1 segments were amplified from all samples, as well as mtDNA 4834 deletions (3) The incidence of mtDNA 4834 deletions in hearing organs of hypercholesteremia rats was significantly higher than that of the control group ( P <0 05) Conclusion Extended hypercholesteremia can induce hearing loss, and mtDNA 4834 deletion in hearing organs may be one of the pathogenic mechanisms