Department of Aerospace Hygiene, School of Aerospace Medicine, Air Force Medical University, Xi'an, China.
Medical School of Chinese PLA, Beijing, China.
Environ Sci Pollut Res Int. 2023 Feb;30(9):23965-23981. doi: 10.1007/s11356-022-23504-9. Epub 2022 Nov 4.
Noise pollution has become one of the important social hazards that endanger the auditory system of residents, causing noise-induced hearing loss (NIHL). Oxidative stress has a significant role in the pathogenesis of NIHL, in which the silent information regulator 1(SIRT1)/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway is closely engaged. Ginsenoside Rd (GSRd), a main monomer extract from ginseng plants, has been confirmed to suppress oxidative stress. Therefore, the hypothesis that GSRd may attenuate noise-induced cochlear hair cell loss seemed promising. Forty-eight male guinea pigs were randomly divided into four groups: control, noise exposure, GSRd treatment (30 mg/kg Rd for 10d + noise), and experimental control (30 mg/kg glycerol + noise). The experimental groups received military helicopter noise exposure at 115 dB (A) for 4 h daily for five consecutive days. Hair cell damage was evaluated by using inner ear basilar membrane preparation and scanning electron microscopy. Terminal dUTP nick end labeling (TUNEL) and immunofluorescence staining were conducted. Changes in the SIRT1/PGC-1α signaling pathway and other apoptosis-related markers in the cochleae, as well as oxidative stress parameters, were used as readouts. Loss of outer hair cells, more disordered cilia, prominent apoptosis, and elevated free radical levels were observed in the experimental groups. GSRd treatment markedly mitigated hearing threshold shifts, ameliorated outer hair cell loss and lodging or loss of cilia, and improved apoptosis through decreasing Bcl-2 associated X protein (Bax) expression and increasing Bcl-2 expression. In addition, GSRd alleviated the noise-induced cochlear redox injury by upregulating superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, decreasing malondialdehyde (MDA) levels, and enhancing the activity of SIRT1 and PGC-1α messenger ribonucleic acid (mRNA) and protein expression. In conclusion, GSRd can improve structural and oxidative damage to the cochleae caused by noise. The underlying mechanisms may be associated with the SIRT1/PGC-1α signaling pathway.
噪声污染已成为危害居民听觉系统的重要社会危害之一,导致噪声性听力损失(NIHL)。氧化应激在 NIHL 的发病机制中起着重要作用,沉默信息调节因子 1(SIRT1)/增殖物激活受体-γ共激活因子 1α(PGC-1α)信号通路与之密切相关。人参皂苷 Rd(GSRd)是从人参植物中提取的主要单体之一,已被证实可抑制氧化应激。因此,GSRd 可能减轻噪声引起的耳蜗毛细胞损失的假设似乎很有希望。48 只雄性豚鼠随机分为四组:对照组、噪声暴露组、GSRd 治疗组(30mg/kg Rd 治疗 10d+噪声)和实验对照组(30mg/kg 甘油+噪声)。实验组每天接受 115dB(A)军用直升机噪声暴露 4 小时,连续 5 天。通过内耳基底膜制备和扫描电子显微镜评估毛细胞损伤。进行末端 dUTP 缺口末端标记(TUNEL)和免疫荧光染色。作为读出,耳蜗中 SIRT1/PGC-1α 信号通路和其他凋亡相关标志物的变化以及氧化应激参数。在外毛细胞丢失、纤毛更加紊乱、明显凋亡和自由基水平升高的情况下观察到实验组。GSRd 治疗显著减轻听力阈移,改善外毛细胞丢失和纤毛倒伏或丢失,并通过降低 Bcl-2 相关 X 蛋白(Bax)表达和增加 Bcl-2 表达来改善凋亡。此外,GSRd 通过上调超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平、降低丙二醛(MDA)水平以及增强 SIRT1 和 PGC-1α 信使核糖核酸(mRNA)和蛋白表达来减轻噪声引起的耳蜗氧化还原损伤。总之,GSRd 可以改善噪声引起的耳蜗结构和氧化损伤。其潜在机制可能与 SIRT1/PGC-1α 信号通路有关。