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黄芪甲苷对变应性鼻炎模型小鼠改善作用的机制初探                                                            Δ


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        陈旭青 ,马华安 ,周龙云 ,严道南 ,刘书芬 ,吴继勇(1.南京中医药大学附属医院耳鼻喉科,南京 210029;
        2.南京医科大学第一附属医院康复科,南京 210029;3.上海中医药大学附属龙华医院基础部,上海 210032)
        中图分类号 R765.2;R285.5        文献标志码 A           文章编号     1001-0408(2021)10-1187-09
        DOI  10.6039/j.issn.1001-0408.2021.10.06
        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0.02 mL/g腹腔注射黄芪甲苷40 mg/kg(第21~27天均于攻击致敏前1 h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24 h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。
        关键词 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

        Preliminary Study on the Improvement Effects of Astragaloside Ⅳ on Allergic Rhinitis Model Mice
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        CHEN Xuqing ,MA Huaan ,ZHOU Longyun ,YAN Daonan ,LIU Shufen ,WU Jiyong (1. Dept. of
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        Otorhinolaryngology,the Affiliated Hospital of Nanjing University of TCM,Nanjing 210029,China;2. Dept.
        of Rehabilitation,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;3. Faculty
        of Basic Medicine,Longhua Hospital Affiliated to Shanghai University of TCM,Shanghai 210032,China)
        ABSTRACT    OBJECTIVE:To preliminarily study 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 JAK2 and STAT6 proteins in
        spleen tissue(i.e. p-JAK2/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-JAK2
        and p-STAT6 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-JAK2 and p-STAT6 positive cellsin the nasal mucosa and spleen
        tissue as well as the p-JAK2/JAK2 ratio and p-STAT6/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). CONCLUSIONS:Astragaloside Ⅳ can effectively
                                                           improve the inflammatory response in AR model mice,the
           Δ 基金项目:国家自然科学青年科学基金资助项目(No.81804152)
           *住院中医师,硕士。研究方向:中西医结合防治变应性鼻炎。                    mechanism of which may be related to down-regulation of
        E-mail:975771017@qq.com                            JAK2/STAT6 signaling pathway and ROS level.
           # 通信作者:主任医师,教授,硕士生导师,博士。研究方向:中西                 KEYWORDS      Allergic rhinitis;Astragaloside Ⅳ ; ROS;
        医结合防治耳鼻喉科多发病、疑难病。E-mail:houhuty@163.com            JAK2/STAT6 signaling pathway;Mice


        中国药房    2021年第32卷第10期                                            China Pharmacy 2021 Vol. 32 No. 10  ·1187 ·
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