Department of Otolaryngology, GuangDong Women and Children Hospital, Guangzhou, Guangdong, China.
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
J Radiat Res. 2021 Mar 10;62(2):217-225. doi: 10.1093/jrr/rraa137.
The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells.
本研究旨在通过建立小鼠模型来确定褪黑素是否可以保护内耳免受辐射损伤。将 81 只 4 周龄的 Balb/c 小鼠随机分为五组:对照组;50mg/kg 褪黑素组;5mg/kg 褪黑素+放射治疗组;50mg/kg 褪黑素+放射治疗组;放射治疗组。放射治疗组接受 16Gy 照射,照射前 30min 经腹腔注射褪黑素。照射后第 3、7 天,通过听性脑干反应(ABR)和畸变产物耳声发射(DPOAE)测试评估外毛细胞功能,通过光镜观察内耳细胞的病理变化,并测定 prestin mRNA 的表达。放射治疗后 ABR 阈值升高,波 I 潜伏期延长,但褪黑素组的增加幅度较低(P<0.05)。DPOAE 显示 8-12kHz 处存在放射治疗引起的听力损失,且第 7 天的听力损失大于第 3 天。但褪黑素组的听力损失较小(P<0.05)。组织病理学检查显示照射导致耳蜗基底膜破裂和扭曲、血管纹破坏以及外毛细胞肿胀。褪黑素减轻了这些变化。放射治疗上调了 prestin mRNA 的表达。褪黑素组中放射治疗诱导的 prestin 上调减少(P<0.05),且 50mg/kg 褪黑素组减少更明显(P<0.05)。褪黑素通过减少外毛细胞损伤来保护内耳免受辐射损伤。