miR-375在变应性鼻炎小鼠鼻黏膜上皮细胞凋亡中的调控作用  

Regulation of miR-375 on apoptosis and inflammatory response in nasal mucosa of allergic rhinitis mice

作　　者：汪涛[1] 王珮华[1] 陈东[1] 李莹 WANG Tao;WANG Peihua;CHEN Dong;LI ying(Department of Otorhinolaryngology Head and Neck Surgery,Shanghai Ninth People's Hospital,School of Medicine,Shanghai Jiao Tong University,Ear Institude Shanghai Jiao Tong Univerity School of Medicine,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases,Shanghai,200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院耳鼻咽喉头颈外科,上海交通大学医学院耳科学研究所,上海市耳鼻疾病转化医学重点实验室 [2]上海交通大学医学院附属第一人民医院宝山分院

出　　处：《中国中西医结合耳鼻咽喉科杂志》2020年第2期103-108,115,共7页Chinese Journal of Otorhinolaryngology in Integrative Medicine

摘　　要：目的探讨miR-375在变应性鼻炎小鼠鼻黏膜上皮细胞凋亡和炎症反应中的调控作用。方法运用卵清蛋白(OVA)致敏的小鼠变应性鼻炎模型,使用实时定量PCR(qRT-PCR)、蛋白质印迹试验(Western Blot)、酶联免疫吸附试验(ELISA)、免疫组织化学检测鼻黏膜上皮细胞内miR-375、JAK2、细胞凋亡相关蛋白(JAK2蛋白,裂解的蛋白酶3(Cleaved caspase 3),聚[ADP-核糖]聚合酶裂解酶(Cleaved PARP),蛋白酶3(Caspase 3),聚[ADP-核糖]聚合酶(PARP),p-STAT3蛋白,STAT3蛋白和β肌动蛋白(β-actin))和血浆IL-6、TNF-α、IL-10的表达水平。结果miR-375在变应性鼻炎小鼠的鼻黏膜上皮细胞中表达降低,而JAK2表达增高;JAK2蛋白、p-STAT3蛋白和裂解的蛋白酶3均在OVA组表达增高;给OVA致敏的变应性鼻炎小鼠注射miR-375模拟物可以导致血清IL-6、TNF-α的分泌下降,而IL-10分泌增加,该作用可以被带有过表达JAK2的腺病毒感染后而减弱。结论miR-375/JAK2调控通路存在于变应性鼻炎鼻黏膜上皮细胞中,并通过JAK2/STAT3信号通路调控细胞的凋亡和炎症反应,miR-375在变应性鼻炎的病程中有保护性机制。Objective This study aims to investigate the role of miR-375 in the regulation of apoptosis and inflammatory response in nasal mucosal epithelial cells of allergic rhinitis mice.Method Allergic rhinitis mice model sensitized with ovalbumin(OVA),and using real-time quantitative PCR(qRT-PCR),Western Blot,enzyme-linked immunosorbent assay(ELISA),immunohistochemistry to detect miR-375,JAK2,apoptosis-related proteins(JAK2 protein、Cleaved caspase 3、Cleaved PARP,、Caspase 3、PARP、p-STAT3、STAT3 andβ-actin)and IL-6,TNF-α,IL-10 expression levels in plasma.Results MiR-375 expression was found to be decreased in nasal mucosal epithelial cells of allergic rhinitis mice,while JAK2、JAK2 protein、p-STAT3 protein and cleaved caspase 3 expression exhibited an opposite effect.Injection of miR-375 agomir following ovalbumin(OVA)treatment declined OVA-induced allergic rhinitis,characterized as the down-regulation of IL-6 and TNF-αsecretion,and up-regulation of IL-10 secretion,these effects were declined by infection with JAK2 adenovirus through nasal cavity inhalation.Conclusion miR-375/JAK2 regulatory pathway is identified in nasal mucosal epithelial cells of allergic rhinitis,and regulates apoptosis and inflammatory response through JAK2/STAT3 signaling pathway.MiR-375 has a protective mechanism in allergic rhinitis.

关 键 词：变应性鼻炎 卵清蛋白 miR-375、细胞凋亡 

分 类 号：R765.21[医药卫生—耳鼻咽喉科] R-332[医药卫生—临床医学]