Tanigawa T, Shibata R, Ouchi N, Kondo K, Ishii M, Katahira N, Kambara T, Inoue Y, Takahashi R, Ikeda N, Kihara S, Ueda H, Murohara T
Department of Otolaryngology, Aichi Medical University, Aichi, Japan.
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cell Death Dis. 2014 Apr 24;5(4):e1189. doi: 10.1038/cddis.2014.140.
Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.
肥胖相关疾病与年龄相关性听力减退（ARHI）的发生密切相关。脂联素（APN）对包括内皮功能障碍和动脉粥样硬化在内的肥胖相关病症具有保护作用。在此，我们研究了APN对ARHI的影响。与野生型（WT）小鼠相比，APN基因敲除（APN-KO）小鼠的听力减退加剧，尤其是在高频范围。补充APN可预防APN-KO小鼠的听力减退。在2月龄时，与WT小鼠相比，APN-KO小鼠的耳蜗血流和血管纹（SV）的毛细血管密度显著降低。2月龄的APN-KO小鼠耳蜗的柯蒂氏器中末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性凋亡细胞也显著增加。在6月龄时，APN-KO小鼠的柯蒂氏器中毛细胞丢失。在培养的听觉HEI-OC1细胞中，APN降低了缺氧条件下的凋亡活性。临床上，ARHI患者的血浆APN水平显著较低。多因素logistic回归分析确定APN是ARHI的一个重要且独立的预测因子。我们的观察结果表明，APN在预防ARHI中具有重要作用。
