咖啡因通过下调小鼠炎症通路改善年龄相关性听力损失。
Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice.
机构信息
Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Binzhou Medical University Hospital, Binzhou, China.
Shandong Binzhou Animal science and veterinary Medicine Academy, Binzhou, China.
出版信息
Otol Neurotol. 2024 Mar 1;45(3):227-237. doi: 10.1097/MAO.0000000000004098. Epub 2024 Feb 2.
OBJECTIVE
Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism.
METHODS
Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot.
RESULTS
The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1β, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae.
CONCLUSIONS
Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.
目的
年龄相关性听力损失（ARHL），又称老年性聋，是一种使人衰弱的感觉损伤，影响老年人群。目前尚无治疗 ARHL 的理想方法。长期摄入咖啡因在许多疾病中都有抗衰老作用。本研究旨在确定咖啡因是否能改善小鼠的 ARHL，并分析其机制。
方法
从 3 个月到 12 个月大，将咖啡因添加到 C57BL/6J 小鼠的饮用水中。在实验过程中监测小鼠的体重、食物摄入量和水摄入量。通过 ELISA 检测血清代谢指标。通过 ABR 和耳蜗苏木精-伊红染色评估听觉系统功能。通过 Q-PCR、免疫荧光和 Western blot 检测基因表达。
结果
结果表明，与年轻小鼠相比，ARHL 小鼠表现出听力受损和耳蜗组织损伤。然而，咖啡因治疗的 ARHL 小鼠表现出听力和耳蜗组织形态的改善。与年轻小鼠相比，ARHL 小鼠耳蜗中炎症相关基因（如 TLR4、Myd88、NF-κB 和 IL-1β）的表达显著增加，但在咖啡因处理的耳蜗中则下调。
结论
炎症参与了小鼠的 ARHL，长期补充咖啡因可以通过下调 TLR4/NF-κB 炎症途径来改善 ARHL。我们的研究结果为预防 ARHL 提供了新的思路，并为 ARHL 治疗提供了新的药物靶点。
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