基于血清激素水平和基因差异性表达探讨老年性聋与中医肾虚的相关性及其物质基础

Study on correlation and the material basis between age-related hearing loss and 'kidney deficiency' in TCM based on serum hormone level and differential gene expression

目的:探讨中医肾虚与老年性聋的相关性及其物质基础。方法:纯音测听检测听功能;肾虚症状评分表测定研究对象肾虚积分;化学发光法检测血清甲状腺激素(T3、T4)、促肾上腺皮质激素(ACTH)和皮质醇含量;基因表达谱芯片检测全基因组基因表达,筛选差异表达基因;实时定量PCR验证差异表达基因。结果:老年性聋组患者肾虚积分明显高于对照组(P<0.01),Pearson相关分析表明肾虚积分与听阈呈正相关,相关系数为0.766,P=0.000。老年性聋组血清T3和T4水平与对照组比较有下降趋势,但无统计学意义;ACTH和皮质醇水平明显低于对照组,且差异有统计学意义(P<0.01,P<0.05)。基因表达谱芯片检测结果显示,糖皮质激素受体调节相关基因RGS2、ARL8B、IL11RA、Cdc42和TSC22D3表达有明显变化,实时PCR检测结果显示,老年性聋组TSC22D3基因表达明显低于对照组(P<0.05),表达水平为对照组的0.2倍。结论:老年人听力损失与肾虚积分呈正相关,糖皮质激素及其受体是中医肾虚与老年性聋相关的物质基础之一,其中TSC22D3基因发挥重要作用。

Objective： To investigate the correlation between ＇kidney deficiency＇ and age-related hearing loss （ARHL） and the material basis. Methods： Hearing function was examined by pure tone test. The ＇kidney deficiency＇ accumulate points were got by questionnaire about ＇kidney deficiency＇ symptoms. T3, T4, ACTH and cortisol levels in serum were tested by chemiluminescence. The gene expression profile was examined by human genechip. Real-time quantitative PCR （qPCR） verified the differently expressed genes. Results： The ＇kidney deficiency＇ accumulate point of ARHL group was higher than that of control group. Pearson correlation analysis showed that ＇kidney deficiency＇ accumulate point was positively correlated with hearing threshold value（r=0.766, P=0.000）. The levels of T3 and T4 were lower than control group, but had no significant difference. The levels of ACTH and cortisol in ARHL group were lower than that of control group （P〈0.01, P〈0.05）. The gene expression profile analysis showed that the expressions of many glucocorticdid receptor target genes such as RGS2, ARL8B, ILllRA, Cdc42 and TSC22D3 had significant difference between ARHL group and control group. Real-time PCR showed that TSC22D3 expression in ARHL group was five times lower than that of control group significantly （P〈0.05）. Conclusion： The glucocorticoid and its receptors may be the material basis of the correlation between the ＇kidney deficiency＇ and ARHL. In addition, TSC22D3 gene play an important role.