动物模型研究炎症小体在海水淹溺诱发过敏性鼻炎中的作用  

Roles of inflammasome activation in allergic rhinitis induced by seawater drowning

作　　者：周烨 郏凯威 李云晖 侯晋 杨子轩 Zhou Ye;Jia Kaiwei;Li Yunhui;Hou Jin;Yang Zixuan(Institute of Immunology,Basic Medical School,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学基础医学院免疫学研究所,上海200433 [2]联勤保障部队第九四〇医院

出　　处：《海军医学杂志》2023年第4期383-387,共5页Journal of Navy Medicine

基　　金：军队青年科技英才(2020QN06119);联勤保障部队第九四〇医院面上项目(2021yxky061)。

摘　　要：目的探讨炎症小体在小鼠海水淹溺诱发过敏性鼻炎(seawater drowning induced allergic rhinitis,SW⁃AR)发病过程中的作用。方法选取Balb/c雄性小鼠15只,按数字表法随机分为对照组、SW⁃AR组和抑制剂组3组,每组5只。构建小鼠模型,观察并记录10 min小鼠挠鼻和喷嚏次数;收集鼻黏膜组织,HE染色观察组织结构;定量PCR法检测白细胞介素(IL)⁃6、IL⁃1β、IL⁃18 mRNA表达水平;Western blotting法检测炎症小体下游含半胱氨酸的天冬氨酸蛋白水解酶⁃1(caspase⁃1)和gasdermin D(GSDMD)的活化;收集血清,酶联免疫吸附(enzyme linked immunosorbent assay,ELISA)法检测IL⁃18蛋白水平。结果SW⁃AR模型构建成功,与对照组相比,SW⁃AR组小鼠挠鼻和喷嚏次数明显多于对照组(P<0.01)。与对照组小鼠相比,SW⁃AR组小鼠鼻黏膜内炎症细胞因子(IL⁃6、IL⁃1β、IL⁃18)水平明显升高(P<0.01),血清内IL⁃18水平升高(P<0.01),同时炎症小体活化程度(鼻黏膜组织内caspase⁃1和GSDMD活化)增强。使用炎症小体活化抑制剂处理后,小鼠挠鼻和喷嚏症状得到有效缓解,与SW⁃AR组相比,抑制剂组小鼠鼻黏膜炎症细胞因子(IL⁃6、IL⁃1β、IL⁃18)水平降低(P<0.01),血清IL⁃18水平降低(P<0.01),同时炎症小体活化程度(鼻黏膜组织内caspase⁃1和GSDMD活化)有所缓解。结论SW⁃AR小鼠鼻黏膜组织内炎症小体过度活化,加重病情,给予炎症小体活化抑制剂治疗后可有效缓解SW⁃AR行为学症状,减轻局部炎症反应。Objective To investigate the roles of inflammasome on the onset of allergic rhinitis(AR)induced by seawater drowning.Methods 15 Balb/c male mice were used in the experiment,and were randomly divided into the control group,the seawater drowning⁃induced allergic rhinitis group(or simply the SW⁃AR group)and the inhibition agent group,each consisting of 5 animals.Following development of the model,the times of nose scratching and sneezing within 10 minutes were closely observed and recorded.Nasal mucosal tissues were collected and tissue structures were observed by HE staining.The mRNA expression levels of IL⁃6,IL⁃1βand IL⁃18 were detected by quantitative RT⁃PCR.The activation of caspase⁃1 and GSDMD was detected by Western blotting.The serum level of IL⁃18 was measured by enzyme⁃linked immunosorbent assay(ELISA).Results The SW⁃AR model was successfully established.Compared with those of the control group,the nose scratching and sneezing symptoms in the SW⁃AR group were obviously stronger than those of the control group(P<0.01).As compared with those of the control group,the levels of inflammatory factors(IL⁃6,IL⁃1β,IL⁃18)in the SW⁃AR group significantly increased(P<0.01),and the serum level of IL⁃18 also increased(P<0.01).At the same time,the activation of inflammasome(caspase⁃1 and GSDMD)in the nasal mucosal tissue elevated as well.Following treatment with inflammasome activation,the nose scratching and sneezing symptoms markedly alleviated.As compared with those of the SW⁃AR group,inflammatory factor levels(IL⁃6,IL⁃1β,IL⁃18)in the inhibition agent group all decreased(P<0.01),the serum level of IL⁃18 also decreased(P<0.01)and the inflammasome activation as well as inflammatory response in nasal mucosal tissues and AR symptoms were also relieved.Conclusion Inflammasome activation in the SW⁃AR model could deteriorate the illness conditions of mice,the inflammasome inhibitor treatment could effectively alleviate the symptoms of AR and reduce local inflammatory responses.

关 键 词：海水淹溺 过敏性鼻炎 炎症小体 治疗 

分 类 号：R392.8[医药卫生—免疫学] R828.6[医药卫生—基础医学]