Zhou F W, Zhang T, Jin Y, Ma Y F, Xian Z P, Wu Z M, Yu G D
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.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Apr 7;57(4):433-441. doi: 10.3760/cma.j.cn115330-20210629-00383.
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. 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. 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 <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 <0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all <0.05). 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.
探讨NLRP3介导的细胞焦亡与变应性鼻炎(AR)嗅觉功能障碍(OD)之间的关系,并评估选择性NLRP3抑制剂CY-09对OD的治疗潜力。用卵清蛋白建立AR小鼠模型,通过埋藏食物颗粒试验检测AR小鼠的嗅觉功能。对有OD的小鼠腹腔注射CY-09或生理盐水。通过免疫组织化学检测嗅球中小胶质细胞和星形胶质细胞的激活情况。通过蛋白质免疫印迹法检测细胞焦亡相关蛋白的表达水平。通过实时聚合酶链反应测定细胞焦亡相关促炎因子mRNA的水平。采用SPSS 24.0软件进行统计分析。试验后,卵清蛋白成功建立了AR小鼠模型,其中52.5%(21/40)表现出OD。OD组嗅球组织中激活的小胶质细胞和星形胶质细胞数量多于非OD组(均P<0.05)。与对照组相比,OD组嗅球中NLRP3、半胱天冬酶-1和gasdermin D(GSDMD)的表达显著增加(均P<0.05)。CY-09可显著降低NLRP3、半胱天冬酶-1、GSDMD、白细胞介素-1β和白细胞介素-18的表达水平,并抑制嗅球组织中小胶质细胞和星形胶质细胞的激活(均P<0.05)。NLRP3介导的细胞焦亡与AR相关的OD密切相关。CY-09可改善AR小鼠的嗅觉功能,这可能与阻断NLRP3介导的细胞焦亡有关。