摘要
目的 探究益气聪明汤加减方对药源性及老年性耳聋的防治作用并初步探索其作用机制。方法 采用斑马鱼模型,利用卡那霉素、顺铂和过氧化氢(H2O2)建立毛细胞损伤模型,统计毛细胞荧光面积来评价益气聪明汤加减方的毛细胞保护作用。利用豚鼠动物模型,通过卡那霉素、顺铂和D-半乳糖建立豚鼠耳聋模型,检测听力阈值变化和观察耳蜗基底膜毛细胞来评价益气聪明汤加减方的防治作用。通过网络药理学初步探究其作用机制。结果 斑马鱼模型中,益气聪明汤加减方质量浓度在1.0~2.0 mg/mL时,能显著降低卡那霉素、顺铂和H2O2诱导的毛细胞损伤(P<0.05,P<0.01);豚鼠模型中,益气聪明汤加减方高剂量组能显著降低卡那霉素、顺铂和D-半乳糖诱导的听力损失(P<0.01),低剂量组能显著降低D-半乳糖诱导的听力损失(P<0.01);网络药理学筛选出5个主要活性成分、5个核心靶点、915个GO条目、153条KEGG通路,包括AGE-RAGE信号通路、MAPK信号通路等。结论 益气聪明汤加减方对药源性及老年性耳聋能起到明显的防治作用,其机制可能与调控AGE-RAGE信号通路、MAPK信号通路等相关。
Objective To investigate the preventive and therapeutic effects and mechanisms of the modified Yiqi Congming decoction on drug-induced and age-related hearing loss.Methods A zebrafish model was employed to establish a hair cell damage model induced by kanamycin,cisplatin,and hydrogen peroxide.The protective effect of modified Yiqi Congming decoction on hair cells was evaluated by quantifying the fluorescent area of the hair cells.A guinea pig model of hearing loss was established by using kanamycin,cisplatin,and D-galactose.The effects of Yiqi Congming decoction were evaluated by detecting changes in hearing threshold and observing hair cells in the cochlear basement membrane.The mechanisms were preliminarily explored through network pharmacology.Results In zebrafish model,the decoction significantly reduced hair cell damage induced by kanamycin,cisplatin,and hydrogen peroxide at concentrations of 1.0~2.0 mg/mL(P<0.05,P<0.01).In the guinea pig model,the high-dose group of the decoction significantly alleviated hearing loss induced by kanamycin,cisplatin,and D-galactose(P<0.01),while the low-dose group notably reduced D-galactose-induced hearing loss (P<0.01). Network pharmacology identified five main active components, five core targets, 915 GO entries, and153 KEGG pathways, including the AGE-RAGE signaling pathway and the MAPK signaling pathway. ConclusionModified Yiqi Congming decoction exhibits significant preventive and therapeutic effects on drug-induced andage-related hearing loss, potentially through modulating pathways such as AGE-RAGE and MAPK signaling.
作者
陈伟强
杨艾霖
林粤圣
余冲
袁旭江
温露
张明
陈钢
CHEN Weiqiang;YANG Ailin;LIN Yuesheng;YU Chong;YUAN Xujiang;WEN Lu;ZHANG Ming;CHEN Gang(Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations,Center for Drug Research and Development,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Sunho Pharmaceutical Co.Ltd,Zhongshan 528437,China)
出处
《广东药科大学学报》
2025年第1期99-107,共9页
Journal of Guangdong Pharmaceutical University
基金
国家自然科学基金项目(82474092)
广州市重点研发计划项目(2023B03J1293)
粤澳科技创新联合资助项目(2022A0505020014)
广东药科大学大学生创新训练计划立项项目(S202410573005X,202410573007X)。
关键词
益气聪明汤加减方
药源性耳聋
老年性耳聋
网络药理学
modified Yiqi Congming decoction
drug-induced hearing loss
age-related hearing loss
network pharmacology
作者简介
陈伟强(1999-),男,硕士研究生,从事防治耳聋药物及制剂研究,Email:981952358@qq.com;通信作者:陈钢(1978-),男,教授,主要从事中西药物新剂型及创新药物研发,Email:cg753@126.com。
