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葛根素通过抑制线粒体依赖性细胞凋亡通路缓解庆大霉素的耳毒性。

Puerarin alleviates the ototoxicity of gentamicin by inhibiting the mitochondria‑dependent apoptosis pathway.

机构信息

Department of Otolaryngology‑Head and Neck Surgery, Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Department of Otolaryngology‑Head and Neck Surgery, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China.

出版信息

Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12491. Epub 2021 Oct 15.

Abstract

Gentamicin (GM) is a commonly used antibiotic, and ototoxicity is one of its side effects. Puerarin (PU) is an isoflavone in kudzu roots that exerts a number of pharmacological effects, including antioxidative and free radical scavenging effects. The present study investigated whether PU could protect against GM‑induced ototoxicity in C57BL/6J mice and House Ear Institute‑Organ of Corti 1 (HEI‑OC1) cells. C57BL/6J mice and HEI‑OC1 cells were used to establish models of GM‑induced ototoxicity in this study. Auditory brainstem responses were measured to assess hearing thresholds, and microscopy was used to observe the morphology of cochlear hair cells after fluorescent staining. Cell viability was examined with Cell Counting Kit‑8 assays. To evaluate cell apoptosis and reactive oxygen species (ROS) production, TUNEL assays, reverse transcription‑quantitative PCR, DCFH‑DA staining, JC‑1 staining and western blotting were performed. PU protected against GM‑induced hearing damage in C57BL/6J mice. PU ameliorated the morphological changes of mouse cochlear hair cells and reduced the apoptosis rate of HEI‑OC1 cells after GM‑mediated damage. GM‑induced ototoxicity may be closely related to the upregulation of p53 expression and the activation of endogenous mitochondrial apoptosis pathways, and PU could protect cochlear hair cells from GM‑mediated damage by reducing the production of ROS and inhibiting the mitochondria‑dependent apoptosis pathway.

摘要

庆大霉素(GM)是一种常用的抗生素,耳毒性是其副作用之一。葛根素(PU)是葛根中的一种异黄酮,具有多种药理作用,包括抗氧化和清除自由基作用。本研究旨在探讨葛根素(PU)是否可以预防 GM 诱导的 C57BL/6J 小鼠和 House Ear Institute-Organ of Corti 1(HEI-OC1)细胞耳毒性。在这项研究中,使用 C57BL/6J 小鼠和 HEI-OC1 细胞建立 GM 诱导的耳毒性模型。通过听觉脑干反应测量评估听力阈值,并用荧光染色观察耳蜗毛细胞的形态。通过 Cell Counting Kit-8 测定法检查细胞活力。为了评估细胞凋亡和活性氧(ROS)的产生,进行 TUNEL 测定、逆转录-定量 PCR、DCFH-DA 染色、JC-1 染色和 Western blot 分析。PU 可预防 GM 诱导的 C57BL/6J 小鼠听力损伤。PU 改善了 GM 介导的损伤后小鼠耳蜗毛细胞的形态变化,并降低了 HEI-OC1 细胞的凋亡率。GM 诱导的耳毒性可能与 p53 表达上调和内源性线粒体凋亡途径的激活密切相关,而 PU 可以通过减少 ROS 的产生和抑制线粒体依赖性凋亡途径来保护耳蜗毛细胞免受 GM 介导的损伤。

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