白细胞介素1受体拮抗剂对大鼠过敏性哮喘的治疗作用及相关机制研究  

Effects of interleuidn 1 receptor antagonist on allergy asthma in rat model and its mechanism

作　　者：刘中成[1] 王园园[2] 邹民吉[2] 王嘉玺[2] 徐东刚[2] 

机构地区：[1]河北大学药学院,保定071002 [2]军事医学科学院基础医学研究所

出　　处：《中华医学杂志》2008年第34期2432-2436,共5页National Medical Journal of China

基　　金：国家科技支撑计划基金资助项目（2006BAI19B05-3）

摘　　要：目的研究白细胞介素1受体拮抗剂（IL-1ra）对大鼠过敏性哮喘的治疗作用及相关机制。方法雌性SD大鼠分为正常对照组、哮喘模型组、哮喘模型低剂量IL-1ra（6mg／kg）治疗组（低剂量治疗组）和高剂量IL-1ra（30mg／kg）治疗组（高剂量治疗组），每组10只。采用卵白蛋白腹腔及皮下注射致敏加雾化吸入激发的方法建立大鼠过敏性哮喘模型。激发前尾静脉注射不同剂量的IL—1ra。通过检测各组大鼠肺功能、肺泡灌洗液（BALF）炎性细胞构成、肺组织病理切片、血清总IgE含量等指标评价治疗效果，利用半定量RT—PCR检测信号转导子和转录激活子6（STAT6）mRNA以及核因子KB（NF-κB）mRNA表达情况。结果哮喘模型组大鼠呼吸速率[（206±11）次／min]、呼气流量[（77±8）μl/s]、BALF嗜酸粒细胞比例（24．8％±1．3％）、血清总IgE含量[（72．5±8．1）ng／ml]、STAT6表达（0．294±0．048）和NF-κB表达（0．686±0．052）均明显高于低剂量治疗组[分别为（183±9）次／min，（64±5）μL／s，18．5％±3．1％，（63．4±4．8）ng／ml，0．229±0．038，0．613±0．062，均P〈0．05]和高剂量治疗组[分别为（181±11）次／min，（57±4）μl／s，14．7％±2．1％，（41．4±7．8）ng／ml，0．194±0．076，0．352±0．267，均P〈0．05]。高剂量治疗组治疗效应优于低剂量治疗组（P〈0．05）。肺组织病理检查与以上结果相近。结论IL-1ra对大鼠过敏性哮喘具有明显的治疗效果，这种作用可能是通过同时调控STAT6 mRNA和NF-κB mRNA的表达实现的。Objective To study the effects of interleukin 1 receptor antagonist （IL-Ira） on allergy asthma and its mechanism. Methods Thirty female SD rats underwent intraperitoneal and hypodermic injection of ovalbumin （OVA） on days 1 and 14, and then underwent spraying of OVA aerosol since day 21 for 7 days so as to＇provoke asthma, and then the rats were randomly divided into 3 equal groups： asthma model group, low dose IL-1ra treatment group undergoing intravenous injection of IL-1ra 6 mg/kg before each provocation （low dose treatment group） , and high dose IL-1 ra treatment group undergoing intravenous injection of IL-1ra 30 mg/kg before each provocation（ high dose treatment group）. Another 10 rats were used as normal controls. Twenty-four hours after the last provocation physiological monitoring equipment was used to detect the pulmonary function. Then the rats were killed. Bronchoalveolar lavage fluid （ BALF ） was collected. ELISA was used to detect the serum IgE content. The ratio of inflammatory cells from the BALF was calculated. Microscopy was conducted to observe the histopathology of lung. RT-PCR was used to examine the mRNA expression of NF-κB and signal transducer and activator of the transcription 6 （ STAT6 ）. Results The respiratory rate, expiratory flow, percentage of eosinophils in BALF inflammatory cells, peripheral blood IgE concentration, mRNA expression of STAT6 and NF-κB of the asthma group were （206 ± 11 ） times/min, （77 ± 8 ） μl/s, 24.8 % ± 1.3%, （ 72.5 ± 8.1 ） ng/ml, 0. 294 ± 0. 048, and 0.686 ± 0.052 respectively, all significantly higher than those of the low dose treatment group [ （183 ± 9） times/min, （64 ± 5） μl/s, 18.5% ± 3.1%, （63.4 ± 4.8 ） ng/ml, 0. 229 ± 0. 038, and 0.613 ± 0. 062 respectively, all P〈0.05] and those of the high dose treatment group [ （ 181 ± 11 ） times/min, （57 ±4） μl/s, 14.7% ± 2.1%, （41.4 ± 7.4） ng/ml, 0. 194 ± 0. 076, and 0. 352 ± 0. 267, all P 〈 0.05]. Thetherapeutic effect of high

关 键 词：哮喘 受体 白细胞介素1 细胞内信号肽和蛋白质类 NF-ΚB 

分 类 号：R686[医药卫生—骨科学]