RAGE在哮喘大鼠中的表达及罗红霉素的干预作用  

Expression of RAGE in asthmatic rats and the intervention of Roxithromycin

作　　者：顾晓菲 陈慧君[2] 陈鑫淼 徐挺挺 邱章伟 吴立琴 戴威 应颂敏[4] 戴元荣 Gu Xiaofei;Chen Huijun;Chen Xinmiao;Xu Tingting;Qiu Zhangwei;Wu Liqin;Dai Wei;Ying Songmin;Dai Yuanrong(Department of Respiratory Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China;Department of Respiratory Medicine, Jinhua Municipal Central Hospital, Jinhua 321000, China;Department of Neurology Rehabilitation, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China;Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University, Hangzhou 310058, China)

机构地区：[1]温州医科大学附属第二医院、育英儿童医院呼吸内科,温州325027 [2]金华市中心医院呼吸内科,金华321000 [3]温州医科大学附属第二医院、育英儿童医院神经康复科,温州325027 [4]浙江大学医学院附属第二医院呼吸与危重症医学科,杭州310058

出　　处：《中华医学杂志》2019年第32期2542-2546,共5页National Medical Journal of China

基　　金：国家自然科学基金面上项目(81570027);浙江省自然科学基金(LY16H010007).

摘　　要：目的探讨晚期糖基化终产物受体(RAGE)在哮喘大鼠中的表达及罗红霉素的干预作用。方法将18只雄性无特定病原体动物(SPF)级BrownNorway大鼠,按随机数字表法随机分为正常对照组、哮喘模型组、罗红霉素组各6只。通过卵白蛋白(OVA)+Al(OH)3联合致敏,OVA雾化激发构建大鼠哮喘模型,在每次激发前30min,罗红霉素组予以罗红霉素30mg/kg灌胃,正常对照组和哮喘模型组分别用等体积生理盐水代替。采用酶联免疫吸附测定(ELISA)法检测各组大鼠血清和支气管肺泡灌洗液(BALF)中RAGE、白细胞介素(IL)-4的浓度;HE染色法观察各组大鼠肺组织气道炎症和细胞浸润情况;Image-ProPlus图像分析软件测量并计算支气管壁厚度及平滑肌厚度;Western印迹法检测各组大鼠肺组织RAGE蛋白相对表达量。结果哮喘模型组血清和BALF中RAGE、IL-4浓度显著均高于正常对照组[(494±32)比(327±45)ng/L、(32.4±5.8)比(13.1±2.9)ng/L和(553±38)比(399±56)ng/L、(37.8±3.4)比(19.4±2.5)ng/L](均P<0.01),罗红霉素组血清和BALF中RAGE、IL-4浓度均显著低于哮喘模型组[(438±18)比(494±32)ng/L、(22.8±6.0)比(32.4±5.8)ng/L和(444±42)比(553±38)ng/L、(25.6±4.5)比(37.8±3.4)ng/L](均P<0.05);哮喘模型组支气管壁增厚,管腔狭窄,黏膜皱折明显增多,黏膜下水肿,支气管、血管周围及肺泡腔内大量炎症细胞浸润、聚集;支气管壁厚度、平滑肌厚度明显厚于正常对照组(均P<0.01),罗红霉素组气道炎症及重塑改变优于哮喘模型组(P<0.05);哮喘模型组肺组织RAGE蛋白表达显著高于正常对照组(P<0.01),罗红霉素组肺组织RAGE蛋白表达显著低于哮喘模型组(P<0.01)。各组BALF及血清中RAGE和IL-4表达呈正相关(r=0.782、0.804,均P<0.01);肺组织中RAGE与白细胞总数、嗜酸粒细胞数量及平滑肌厚度呈正相关(r=0.897、0.927、0.860,均P<0.01)。结论哮喘大鼠肺组织、血清和BALF中RAGE表达升高,且与气道炎症及气道重�Objective To observe the expression of the Receptor of Advanced glycation end products (RAGE) in asthmatic rats, and explore the intervention of Roxithromycin. Methods A total of 18 Specific Pathogen Free-class Brown Norway male rats were randomly divided into control group, asthma model group and Roxithromycin group, with 6 rats in each group. The asthmatic model was sensitized by intraperitoneal injection of Ovalbumin (OVA)+Al(OH)3, and challenged with OVA. Rats in Roxithromycin group were given Roxithromycin 30 mg/kg 30 minutes before each challenge. Rats in control group and asthma model group were treated with equal volume of saline. The concentrations of RAGE and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELISA);the pathological changes of lung tissues were observed by HE-staining;the thickness of airway wall and airway smooth muscle were measured by Image-Pro Plus;the relative expression of RAGE in lung tissues were detected by Western blot. Results In asthma model group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously higher than those in control group [(494±32) vs (327±45) ng/L;(32.4±5.8) vs (13.1±2.9) ng/L;(553±38) vs (399±56) ng/L;(37.8±3.4) vs (19.4±2.5) ng/L](all P<0.01);in Roxithromycin group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously lower than those in asthma model group [(438±18) vs (494±32) ng/L;(22.8±6.0) vs (32.4±5.8) ng/L;(444±42) vs (553±38) ng/L;(25.6±4.5) vs (37.8±3.4) ng/L](all P<0.05). In asthma model group, the bronchial wall was thickened, the lumen was narrow, the mucosal wrinkles were significantly increased, edema appeared under the mucosa, and a large number of inflammatory cells infiltrated and aggregated in the bronchi, perivascular and alveolar spaces;the thickness of airway wall and airway smooth muscle were significantly increased than those in control group (P<0.01);in Roxithromycin group, airway inflammation and remodeling were allevi

关 键 词：哮喘 糖基化终产物 高级 罗红霉素 大鼠 

分 类 号：R562.25[医药卫生—呼吸系统]