Van De Water Thomas R, Abi Hachem Ralph N, Dinh Christine T, Bas Esperanza, Haake Scott M, Hoosien Gia, Vivero Richard, Chan Sherry, He Jao, Eshraghi Adrien A, Angeli Simon I, Telischi Fred F, Balkany Thomas J
Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136-1015, USA.
Cochlear Implants Int. 2010 Jun;11 Suppl 1:42-55. doi: 10.1179/146701010X12671178390834.
Dexamethasone (DXM) protects hearing against trauma-induced loss.
in vivo: A guinea pig model of electrode induced trauma (EIT)-induced hearing loss was used to locally deliver dexamethasone. In vitro: TNF-α-challenged organ of Corti explants treated with DXM or polymer-eluted DXM +/- PI3K/Akt/PkB/NFkB inhibitors were used for hair cells count and gene expression studies.
in vivo: local DXM treatment of EIT-animals prevents trauma-induced loss of ABR thresholds that occurs in EIT-animals and EIT-animals treated with the carrier solution (i.e., AP), and prevented loss of auditory hair cells. In vitro: DXM and polymer-eluted DXM were equally effective in protecting hair cells from ototoxic levels of TNF-α Inhibitor treated explants demonstrated that DXM treatment requires both Akt/PKB and NFkB signalling for otoprotection. DXM treatment of explants showed up regulation of anti-apoptosis related genes (i.e., Bcl-2, Bcl-xl) and down regulation of pro-apoptosis related genes (i.e., Bax, TNFR-1).
DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.
地塞米松（DXM）可保护听力免受创伤性损失。
体内实验：使用电极诱导创伤（EIT）所致听力损失的豚鼠模型来局部递送地塞米松。体外实验：用DXM或聚合物洗脱的DXM +/- PI3K/Akt/PkB/NFkB抑制剂处理经TNF-α刺激的柯蒂氏器外植体，用于毛细胞计数和基因表达研究。
体内实验：对EIT动物进行局部DXM治疗可防止创伤引起的ABR阈值损失，而这种损失在EIT动物和用载体溶液（即AP）处理的EIT动物中都会出现，并且可防止听觉毛细胞损失。体外实验：DXM和聚合物洗脱的DXM在保护毛细胞免受TNF-α耳毒性水平影响方面同样有效。抑制剂处理的外植体表明，DXM治疗需要Akt/PKB和NFkB信号传导来实现耳保护作用。DXM处理外植体显示抗凋亡相关基因（即Bcl-2、Bcl-xl）上调，促凋亡相关基因（即Bax、TNFR-1）下调。
DXM通过激活细胞信号分子（如NFkB）发挥其耳保护作用，这些信号分子会改变抗凋亡和促凋亡基因的表达。
