黄芪甲苷对变应性鼻炎模型小鼠改善作用的机制初探
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篇名: 黄芪甲苷对变应性鼻炎模型小鼠改善作用的机制初探
TITLE: Preliminary Study on the Improvement Effects of Astragaloside Ⅳ on Allergic Rhinitis Model Mice
摘要: 目的:初步研究黄芪甲苷对变应性鼻炎(AR)模型小鼠改善作用的可能机制。方法:将C57/BL6小鼠随机分为空白组、模型组和黄芪甲苷组,每组10只。除空白组外,其余大鼠均于第0、7、14、21~27天以卵清蛋白为致敏源进行攻击以复制AR模型。于造模第15~27天,黄芪甲苷组小鼠按0.02mL/g腹腔注射黄芪甲苷40mg/kg(第21~27天均于攻击致敏前1h给药),空白组和模型组小鼠腹腔注射等体积生理盐水,每天1次。末次攻击致敏24h后,观察各组小鼠鼻黏膜组织中炎症细胞的浸润情况,检测其鼻腔灌洗液中白细胞介素4(IL-4)、IL-5、干扰素γ(IFN-γ)含量,鼻黏膜和脾脏组织中活性氧簇(ROS)水平和磷酸化Janus激酶2(p-JAK2)、磷酸化信号转导及转录激活蛋白6(p-STAT6)阳性细胞计数,以及脾脏组织中JAK2、STAT6蛋白的磷酸化水平(即p-JAK2/JAK2比值、p-STAT6/STAT6比值)。结果:与空白组比较,模型组小鼠鼻黏膜组织中炎症细胞(嗜酸粒细胞和肥大细胞)计数,鼻腔灌洗液中IL-4、IL-5含量,鼻黏膜和脾脏组织中ROS水平和p-JAK2、p-STAT6阳性细胞计数,脾脏组织中p-JAK2/JAK2比值、p-STAT6/STAT6比值均显著升高(P<0.05),鼻腔灌洗液中INF-γ含量显著降低(P<0.05)。与模型组比较,黄芪甲苷组小鼠鼻黏膜组织中炎症细胞计数,鼻腔灌洗液中IL-4、IL-5含量,鼻黏膜和脾脏组织中ROS水平和p-JAK2、p-STAT6阳性细胞数量,脾脏组织中p-JAK2/JAK2比值、p-STAT6/STAT6比值均显著降低(P<0.05),鼻腔灌洗液中INF-γ含量显著增加(P<0.05)。结论:黄芪甲苷能够有效改善AR模型小鼠变应性炎症反应,其机制可能与下调JAK2/STAT6信号通路及ROS水平有关。
ABSTRACT: OBJECTIVE:To preliminarily s tudy the potential mechanism of astragaloside Ⅳ on allergic rhinitis (AR)model mice. METHODS :C57/BL6 mice were randomly divided into blank group ,model group and astragaloside Ⅳ group,with 10 mice in each group. Except for blank group ,AR model was prepared by sensitization and challenge with ovalbumin on day 0,7,14 and 21-27. Astragaloside Ⅳ group was given astragaloside Ⅳ 40 mg/kg intraperitoneally at the dose of 0.02 mL/g on the 15th to 27th day of modeling (given the drug 1 h before challenge sensitization on the 21st to 27th day ). Blank group and model group were given constant volume of normal saline intraperitoneally ,once a day. Twenty-four hours after sensitization from the last challenge , the infiltration of inflammatory cells in the nasal mucosa of each group was observed ,and the contents of interleukin 4(IL-4), IL-5 and interferon gamma (IFN-γ)in the nasal lavage fluid were measured. The levels of reactive oxygen species (ROS),and the count of phosphorylated Janus kinase 2(p-JAK2)and phosphorylation signal transduction and activation of transcription protein 6 (p-STAT6)positive cells in the nasal mucosa and spleen as well as the phosphorylation levels of JAK 2 and STAT 6 proteins in spleen tissue (i.e. p-JAK 2/JAK2 ratio,p-STAT6/STAT6 ratio)were also determined. RESULTS :Compared with blank group ,the number of inflammatory cells in the nasal mucosa (eosinophils and mast cells )in the model group ,the contents of IL- 4 and IL- 5 in the nasal lavage fluid ,and the levels of ROS in the nasal mucosa and spleen tissues in the model group ,the count of p-JAK 2 and p-STAT 6 positive cells increased significantly ,the p-JAK2/JAK2 ratio,p-STAT6/STAT6 ratio in the spleen tissue were significantly increased (P<0.05),and the content of INF-γ in the nasal lavage fluid was significantly decreased(P<0.05). Compared with model group ,the count of inflammatory cells infiltrated in the nasal mucosa ,the contents of IL- 4 and IL- 5 in the nasal cavity lavage fluid ,the level of ROS and the number of p-JAK 2 and p-STAT 6 positive cellsin the nasal mucosa and spleen tissue as well as the p-JAK2/JAK2 ratio and p-STAT 6/STAT6 ratio in spleen tissue were decreased significantly (P<0.05),and the content of INF-γ in nasal lavage fluid was significantly increased(P<0.05). CO NCLUSIONS:Astragaloside Ⅳ can effectively improve the inflammatory response in AR model mice ,the mechanism of which may be related to down-regulation of JAK2/STAT6 signaling pathway and ROS level.
期刊: 2021年第32卷第10期
作者: 陈旭青,马华安,周龙云,严道南,刘书芬,吴继勇
AUTHORS: CHEN Xuqing ,MA Huaan ,ZHOU Longyun ,YAN Daonan ,LIU Shufen ,WU Jiyong
关键字: 变应性鼻炎;黄芪甲苷;活性氧簇;Janus激酶2/信号转导及转录激活蛋白6信号通路;小鼠
KEYWORDS: Allergic rhinitis ;Astragaloside Ⅳ ;ROS;
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