年龄相关性听力损失大鼠耳蜗代谢组学的初步研究

Study and Application of Cochlear Metabolomics in Rats with Age-related Hearing Loss

万桓志;陈惠东;杨冰倩;张园园;华清泉

1:武汉大学人民医院耳鼻咽喉头颈外科中心

2:武汉大学耳鼻咽喉头颈外科研究所

摘要
目的 应用大鼠耳蜗代谢组学技术探索年龄相关性听力损失的发生机制。方法 选择2月龄(年轻组)和14月龄(老年组)SD大鼠各15只,通过听性脑干反应(ABR)检测各组大鼠听觉功能;利用HE染色观察两组耳蜗组织形态,并通过流式细胞术检测耳蜗组织氧化应激状态。每组选取5只采用非靶向超高效液相色谱-串联质谱(LC-MS/MS)技术对耳蜗组织进行代谢组学检测,分析衰老耳蜗代谢差异。结果 相较于年轻大鼠,老年大鼠ABR检测8、16、32 kHz纯音及click声反应阈值显著升高(P<0.05),HE染色显示耳蜗衰老相关血管纹萎缩(P<0.05),流式细胞术检测提示氧化应激水平明显升高(P<0.05)。代谢组学检测老年组耳蜗中共鉴定出124种差异代谢物,其中包括鞘氨醇、全反式维生素甲酸、油酰胺在内的16种代谢物显著上调,而嘌呤、牛磺酸、硫胺素、脯氨酸及其衍生物等108种代谢物水平明显降低;提示蛋白质合成与分解、鞘脂代谢、嘌呤代谢、氧化应激相关信号转导、细胞死亡、辅酶生物合成等生理病理机制可能与耳蜗衰老有关。结论 细胞衰老和耳蜗代谢功能失调可能是导致年龄相关性听力损失的重要机制。
关键词
年龄相关性听力损失;代谢组学;耳蜗衰老;氧化应激
基金项目(Foundation):
国家专科疾病诊疗中心建设培育资金(ZX0000000037)
作者
万桓志;陈惠东;杨冰倩;张园园;华清泉
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