NLRP3介导的焦亡在变应性鼻炎嗅觉障碍中的作用研究  

Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis

作　　者：周方伟 张田 金莹 马亦飞 鲜志芃 吴志敏 喻国冻 Zhou Fangwei;Zhang Tian;Jin Ying;Ma Yifei;Xian Zhipeng;Wu Zhimin;Yu Guodong(Department of Clinical Medicine,Guizhou Medical University,Guiyang 550004,China;Department of Otorhinolaryngology Head and Neck Surgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学临床医学院,贵阳550004 [2]贵州医科大学附属医院耳鼻咽喉头颈外科,贵阳550004

出　　处：《中华耳鼻咽喉头颈外科杂志》2022年第4期433-441,共9页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：贵州省科学技术基金 (D2011160)。

摘　　要：目的:探讨NLRP3介导的焦亡与变应性鼻炎(AR)嗅觉障碍(olfactory dysfunction,OD)的关系,并评估选择性NLRP3抑制剂CY-09治疗OD的潜力。方法:使用卵清蛋白建立AR小鼠模型,采用埋藏食物小球实验检测AR小鼠嗅觉功能。对发生OD的小鼠腹腔注射CY-09或生理盐水。采用免疫组织化学法检测嗅球中小胶质细胞和星形胶质细胞的活化情况。采用蛋白免疫印迹法检测焦亡相关蛋白的表达水平。采用实时定量反转录聚合酶链反应法检测焦亡相关促炎因子的mRNA水平。运用SPSS 24.0软件进行统计学分析。结果:经检验,卵清蛋白成功建立AR小鼠模型,其中有52.5%(21/40)的小鼠出现OD。OD组嗅球组织中活化的小胶质细胞和星形胶质细胞数量较非OD组更多( P值均<0.05)。与对照组相比,NLRP3、胱天蛋白酶-1(caspase-1)和焦孔素D(gasdermin D,GSDMD)在OD组嗅球中表达显著升高( P值均<0.05)。CY-09能显著降低嗅球中NLRP3、caspase-1、GSDMD、白细胞介素(IL)-1β和IL-18的表达水平,同时抑制小胶质细胞和星形胶质细胞的活化( P值均<0.05)。 结论:NLRP3介导的焦亡与AR伴随的OD密切相关。CY-09可改善AR小鼠的嗅觉损伤,这可能与阻断NLRP3介导的焦亡有关。Objective To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction(OD)in allergic rhinitis(AR),and to evaluate the therapeutic potential of CY-09,a selective NLRP3 inhibitor for OD.Methods An AR mouse model was established with ovalbumin,and the olfactory function of AR mice was detected by the buried food pellet test.Mice with OD were intraperitoneally injected with CY-09 or saline.The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry.The expression level of pyroptosis associated protein was detected by Western blot.The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR.SPSS 24.0 software was used for statistical analysis.Results After the test,ovalbumin successfully established AR mice model,in which 52.5%(21/40)of them showed OD.The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group(all P<0.05).Compared with the control group,the expression of NLRP3,caspase-1 and gasdermin D(GSDMD)was significantly increased in the olfactory bulb of the OD group(all P<0.05).CY-09 could significantly reduce the level of NLRP3,caspase-1,GSDMD,IL-1βand IL-18 expression,and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues(all P<0.05).Conclusion NLRP3-mediated pyroptosis is closely related to the OD associated with AR.CY-09 could improve the olfactory function in AR mice,which may be related to blocking the NLRP3-mediated pyroptosis.

关 键 词：变应性鼻炎 嗅觉障碍 嗅球 焦亡 神经炎症 

分 类 号：R765.21[医药卫生—耳鼻咽喉科] R765.63[医药卫生—临床医学]