姜黄素衍生物WZ01对哮喘气道炎症介质IL-13和组胺及糖皮质激素受体的影响  

Effects of curcumin derivative WZ01 on asthmatic airway inflammatory mediators IL-13, histamine and glucocorticoid receptor

作　　者：李园[1] 湛美正 叶乐平[1] 葛仁山[2] 李昌崇[1] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童呼吸科,浙江温州325027 [2]温州医科大学附属第二医院育英儿童医院科研中心,浙江温州325027

出　　处：《温州医科大学学报》2016年第7期497-502,共6页Journal of Wenzhou Medical University

基　　金：浙江省自然科学基金资助项目(LY14H010004);浙江省"钱江人才计划"项目(QJD1402012);2015年度温州市高层次人才创新技术重点资助项目

摘　　要：目的：研究姜黄素衍生物WZ01对哮喘气道炎症反应、白细胞介素（IL）-13、组胺及糖皮质激素受体（GR）的影响,探讨WZ01抑制哮喘气道炎症的机制。方法：30只小鼠,随机分为：正常对照组、哮喘组、低剂量WZ01组、中剂量WZ01组、高剂量WZ01组,每组6只。在第21~第27天1%卵清白蛋白（OVA）雾化激发,每次雾化前30 min予腹腔注射相应剂量0.9%氯化钠溶液或WZ01。末次激发24 h内,麻醉并处死小鼠,留取肺组织标本HE染色检测炎症病理改变,留取支气管肺泡灌洗液（BALF）进行细胞分类计数,ELISA法检测IL-13和组胺浓度,Western blot和免疫组织化学染色检测肺组织GR蛋白的表达。结果：与正常对照组比较,哮喘组小鼠气道周围可见明显炎症细胞浸润及黏液分泌,BALF中炎症细胞数量、IL-13及组胺水平均显著升高（P〈0.01）。与哮喘组相比,各剂量WZ01组气道周围炎症细胞浸润及黏液分泌显著减少,BALF中淋巴细胞和嗜酸性粒细胞数量明显减少,BALF中IL-13和组胺浓度显著下降,差异均有统计学意义（P〈0.01）;BALF中淋巴细胞数量与IL-13和组胺浓度均呈显著正相关（r值分别为0.886、0.886,P均〈0.01）,嗜酸性粒细胞数量与IL-13和组胺浓度均呈显著正相关（r值分别为0.897、0.898,P均〈0.01）。Western blot和免疫组织化学染色结果显示,哮喘小鼠肺组织GR表达明显降低,与哮喘组相比,不同剂量WZ01均能显著上调哮喘小鼠肺组织GR表达水平。结论：姜黄素衍生物WZ01可显著抑制哮喘气道炎症细胞浸润和黏液分泌,可能与其降低炎症介质IL-13和组胺浓度及上调哮喘小鼠肺组织GR表达水平有关,WZ01可能有望成为防治哮喘气道炎症的新药。Objective： To investigate the effects of curcumin derivative WZO1 on asthmatic airway inflam-mation, inflammatory mediators IL-13 and histamine, and glucocorticoid receptor （GR）. Methods： Thirty mice were randomly divided into： control group, asthma group, low dose WZ01 group, moderate dose WZ01 group and high dose WZ01 group. Each group was 6 mice, respectively. After sensitized with OVA, the mice were chal- lenging with 1% OVA from the 21th to 27th day. Each mouse was intraperitoneally injected with corresponding drugs or normal saline half an hour before atomizing. After the last challenging, mice were anesthetized and sac- rificed within 24 hours, lung tissues were obtained for detecting inflammatory alteration with hematoxylin-eosin staining, and the BALF for cellular classification and counting and the concentrations of IL-13 and histamine by ELISA assay, the expression of GR in lung tissues was detected with immumohistochemieal staining and Western blot. Results： Compared with the normal control group, HE staining showed massive inflammatory cellular in- filtration and mucous secretion accumulated in the asthma group, ELISA analysis showed significantly increased number of inflammatory cells and concentrations of IL-13 and histamine in the BALF （P〈0.01）. Compared with the asthma group, each dose of WZ01 markedly inhibited the inflammatory cellular infiltration and mucous se- cretion in the airway; In each dose WZ01 group, the number of lymphocytes and eosinophils in BALF were dis- tinctly decreased （P〈0.01）, accompanied by the remarkable decline of the concentrations of IL- 13 and histamine （P〈0.01）; the number of lymphocytes had remarkably positive relationships with the concentrations of IL-13 and histamine in the BALF （r values were 0.886 and 0.886, respectively, P〈0.01）. The number of esoinophils had also remarkably positive relationships with the concentrations of IL-13 and histamine in the BALF （r values were 0.897 and 0.898, respectively, P〈0.01）. The result

关 键 词：哮喘 姜黄素衍生物WZ01 白细胞介素13 组胺 糖皮质激素受体 

分 类 号：R725.6[医药卫生—儿科]