pGlu-Apelin-13酰胺通过调节耳蜗巨噬细胞极化及抑制NLRP3炎症小体活化缓解噪声性听力损失的机制研究OA
Research on the mechanism by which pGlu-Apelin-13 amide alleviates noise-induced hearing loss by regulating cochlear macrophage polarization and inhibiting NLRP3 inflammasome activation
目的 探究pGlu-Apelin-13酰胺对噪声暴露诱发听力损失小鼠的干预作用及其机制.方法 40只C57BL/6J小鼠随机分为对照组、模型组及低、中、高剂量pGlu-Apelin-13酰胺组,每组8只.测定听性脑干反应(ABR)阈值,HE染色观察耳蜗形态,RT-qPCR检测炎症因子IL-10、IL-6、TNF-α及Arg-1的mRNA表达,免疫荧光检测耳蜗基底膜M1/M2型巨噬细胞极化情况,ELISA检测血清IL-1β、IL-18水平,免疫组化及Western blot检测NLRP3、ASC及Caspase-1蛋白表达.结果 与模型组比较,低、中、高剂量pGlu-Apelin13酰胺组小鼠在各频率下的ABR阈值均降低,耳蜗毛细胞及螺旋神经节损伤减轻,IL-10和Arg-1表达上调,IL-6、TNF-α、IL-1β及IL-18水平均降低,耳蜗基底膜中M1型巨噬细胞减少、M2型增加,NLRP3、ASC及Caspase-1蛋白表达均显著下调(P<0.05).除ABR阈值外,其余指标均呈现显著的剂量依赖性(P<0.05).结论 pGlu-Apelin-13酰胺能够减轻噪声暴露诱发的小鼠听力损失,其机制与调节巨噬细胞表型极化、抑制NLRP3炎症小体激活有关.
OBJECTIVE To investigate the intervention effect and mechanism of pGlu-Apelin-13 amide on noise-induced hearing loss in mice.METHODS Forty C57BL/6J mice were randomly divided into a control group,a model group,and low-,medium-,and high-dose pGlu-Apelin-13 amide groups,with eight mice in each group.The auditory brainstem response(ABR)threshold was measured.Cochlear morphology was observed by HE staining.The mRNA expression of inflammatory factors IL-10,IL-6,TNF-α,and Arg-1 was detected by RT-qPCR.The polarization of M1/M2 macrophages in the cochlear basilar membrane was detected by immunofluorescence.Serum IL-1β and IL-18 levels were detected by ELISA.The protein expression of NLRP3,ASC,and Caspase-1 was detected by immunohistochemistry and Western blot.RESULTS Compared with the model group,mice in the low,medium,and high dose pGlu-Apelin-13 amide groups showed decreased ABR thresholds at all frequencies,and reduced damage to cochlear hair cells and spiral ganglia;IL-10 and Arg-1 expression was upregulated,while IL-6,TNF-α,IL-1β,and IL-18 levels were decreased,the number of M1 macrophages and the number of M2 macrophages in the cochlear basilar membrane were reduced;NLRP3,ASC,and Caspase-1 protein expression were all significantly downregulated(P<0.05).Except for the ABR threshold,all other indicators showed significant dose-dependency(P<0.05).CONCLUSION pGlu-Apelin-13 amide can alleviate noise-induced hearing loss in mice,and its mechanism is related to regulating macrophage phenotypic polarization and inhibiting NLRP3 inflammasome activation.
周彩玲;乐燕娜;胡祖应;李勇;朱赛群
杭州市职业病防治院职业病科,浙江 杭州 310014杭州市职业病防治院职业病科,浙江 杭州 310014杭州市职业病防治院职业病科,浙江 杭州 310014杭州市第一人民医院耳鼻咽喉科,浙江 杭州 310006杭州市职业病防治院职业病科,浙江 杭州 310014
听觉丧失,噪声性巨噬细胞pGlu-Apelin-13酰胺巨噬细胞极化NLR家族Pyrin域蛋白3炎症小体
Hearing Loss,Noise-InducedMacrophagespGlu-Apelin-13 amidemacrophage polarizationNLR family pyrin domain protein 3 inflammasome
《中国耳鼻咽喉头颈外科》 2026 (2)
87-92,6
浙江省医药卫生科技项目(2025KY171)浙江省疾病预防控制科技计划项目:(2026JKY191)
评论