Apelin-13 prevents apoptosis in the cochlear tissue of noise-exposed rat via Sirt-1 regulation
Apelin-13 prevents apoptosis in the cochlear tissue of noise-exposed rat via Sirt-1 regulation
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DOI：
10.1016/j.jchemneu.2021.101956
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发表时间：
2021-04-12
影响因子：
2.8
通讯作者：
Niknazar, Somayeh
中科院分区：
文献类型：
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作者：
Khoshsirat, Shahrokh;Abbaszadeh, Hojjat-Allah;Niknazar, Somayeh
噪声性听力损失（NIHL）是后天性听力损失的第二大常见原因。声损伤可通过凋亡途径引起耳蜗毛细胞氧化损伤。爱帕琳肽是一种新发现的神经肽，对神经退行性疾病中的氧化应激具有神经保护作用。我们研究了apelin-13通过调节Sirtuin-1（Sirt-1）对大鼠耳蜗毛细胞和螺旋神经节神经元（SGN）抗声损伤的保护作用。将动物分配至对照组、对照+爱帕琳-13（50或100 μ g/kg，ip）组和噪声暴露组而不进行任何处理或在每次噪声会话之前施用爱帕琳13（50或100 μ g/kg，ip）和EX-527（Sirt-1的抑制剂）。噪声组给予110 dB白色噪声，每次6 h，5 d为1次。评估暴露前后畸变产物耳声发射（DPOAE）和耳蜗超氧化物歧化酶（SOD）活性。Western blot检测耳蜗Sirt-1、cleaved-caspase-3、Bax和Bcl-2蛋白表达。TUNEL染色检测细胞凋亡。免疫荧光法检测HCs和SGNs特异性蛋白的表达。在接受100 μ g/kg apelin-13的噪声暴露组中，DPOAE水平显著改善。在高剂量下，爱帕琳增强了噪声刺激下大鼠耳蜗的SOD水平。Apelin 100显著增加噪声暴露大鼠耳蜗组织中Sirt-1的表达，降低切割型半胱氨酸蛋白酶-3和Bax/Bcl-2的比值。这些发现表明apelin-13在预防噪声引起的耳蜗损伤和听力损失方面具有很好的治疗潜力。
Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 mu g/kg, ip), and noise exposure groups without any treatment or were administered apelin13 (50 or 100 mu g/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 mu g/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss.