武汉大学贺祖宏等研究人员合作发现，抑制cGAS-STING通路减少顺铂诱导的内耳毛细胞损伤。相关论文于2024年12月16日在线发表在《神经科学通报》杂志上。

研究人员旨在探究顺铂诱导的耳毒性分子机制。研究人员建立了顺铂诱导毛细胞丧失的体内外耳毒性模型，结果表明，降低STING水平可以减少炎症因子的表达和毛细胞死亡。

此外，研究人员发现顺铂诱导的线粒体功能障碍伴随着细胞质DNA的释放，而这些DNA可能作为环磷酸鸟苷-AMP合成酶（cGAS）-干扰素基因刺激因子（STING）通路与顺铂诱导听力丧失发病机制之间的关键连接因子。STING的特异性抑制剂H-151减少了毛细胞损伤并改善了顺铂引起的听力丧失。

该研究强调了cGAS-STING通路在顺铂耳毒性中的作用，并提出H-151作为治疗听力丧失的有前景的治疗方案。

据悉，尽管顺铂是广泛使用的化疗药物，但它具有显著的毒性并导致不可逆的听力丧失，限制了其在临床中的应用。

附：英文原文

Title: Inhibition of the cGASSTING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage

Author: Sun, Ying, Zou, Shengyu, Xu, Xiaoxiang, Xu, Shan, Sun, Haiying, Tang, Mingliang, Kong, Weijia, Chen, Xiong, He, Zuhong

Issue&Volume: 2024-12-16

Abstract: Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesisstimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.

DOI: 10.1007/s12264-024-01334-8

Source: https://link.springer.com/article/10.1007/s12264-024-01334-8