Exploring the efficacy of(R)-PFI-2 hydrochloride in mitigating noise-induced hearing loss by targeting NLRP3 inflammasome and NF-κB pathway to reduce inner ear inflammation  

作　　者：Dawei Ren Xuemin Chen Hongdong Liu Menghua Li Liting Zheng Pan Yong Mohe Huang Xi Shi Yice Xu Shujin Chen Yan Zhang Wei Zhu 

机构地区：[1]Department of Otorhinolaryngology,the First Hospital of Jilin University,Changchun,130021,Jilin,China [2]Department of Otorhinolaryngology,No.971 Hospital of People’s Liberation Army Navy,Qingdao,266000,Shandong Province,China [3]Senior Department of Otolaryngology-Head&Neck Surgery,Chinese PLA General Hospital,National Clinical Research Center for Otolaryngologic Diseases,State Key Lab of Hearing Science,Ministry of Education,Beijing Key Lab of Hearing Impairment Prevention and Treatment,Beijing,100083,China [4]Artificial Auditory Laboratory of Jiangsu Province,Xuzhou Medical University,Xuzhou,221000,Jiangsu,China [5]Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou,570228,Hainan Provine,China [6]Song Li’s Academician Workstation of Hainan University,School of Pharmaceutical Sciences,Yazhou Bay,Sanya,572000,Hainan Provine,China [7]Department of Otolaryngology-Head and Neck Surgery,The Central Hospital of Xiaogan,Xiaogan,432000,Hubei,China [8]ENT Department,The People’s Hospital of Rongchang District,Chongqing,402460,China

出　　处：《Journal of Otology》2024年第4期200-206,共7页中华耳科学杂志（英文版）

基　　金：supported by the Science and Technology Development Project of Xuzhou Science and Technology Bureau(KC21249);Science and Technology Development Project of Chongqing(CSTB2022NSCQ-M SX1598);Science and Technology Development Project of Xiaogan(XGKJ2023010010);Scientific Research Startup Foundation of Hainan University;Science and Technology Development Project of Hainan.

摘　　要：Noise-induced hearing loss(NIHL)is primarily driven by inflammatory processes within the cochlea,where noise exposure triggers the activation of the NOD-like receptor protein 3(NLRP3)inflammasome,leading to an inflammatory cascade.The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation.Our findings reveal that(R)-PFI-2 hydrochloride,a selective inhibitor of the SETD7 enzyme,effectively inhibits the activation of the cochlear NF-κB pathway,suppresses the release of proinflammatory factors,and prevents inflammasome assembly.This intervention disrupts the perpetuating cycle of inflammation,thereby alleviating damage to cochlear hair cells attributed to acoustic trauma.Consequently,(R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL,targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.

关 键 词：NIHL (R)-PFI-2 hydrochloride NLRP3 NF-κB SETD7 

分 类 号：R764[医药卫生—耳鼻咽喉科]