摘要
目的探讨1型糖尿病与支气管哮喘之间拮抗关系的可能机制以及胰岛素及其受体在气道变应性炎症中的作用。方法将64只雄性SD大鼠随机分为8组,每组8只A组哮喘组;D组糖尿病组;I组胰岛素组;AD组哮喘+糖尿病组;AI组哮喘+胰岛素组;DI组糖尿病+胰岛素组;ADI组哮喘+糖尿病+胰岛素组;C组对照组。通过腹腔注射链脲菌素溶液的方法复制大鼠1型糖尿病模型;皮下注射卵白蛋白,14d后超声雾化吸入卵白蛋白复制大鼠气道变应性炎症反应模型。检测外周血细胞分类、血糖及血清胰岛素水平;收集支气管肺泡灌洗液行细胞计数、分类;HE染色观察肺脏病理变化;用免疫组化方法观察肺脏胰岛素受体的分布;用半定量RT-PCR测定肺组织胰岛素受体mRNA表达。结果糖尿病组血糖显著高于非糖尿病组,A、AI、ADI组大鼠激发后出现以嗜酸性粒细胞及中性粒细胞细胞增高为主的气道炎症反应。AD组气道炎症反应介于有哮喘组与非哮喘组之间。ADI、AI组、A组胰岛素水平(分别为27mIU/L±8mIU/L;83mIU/L±12mIU/L;71mIU/L±12mIU/L),均高于其相应对照(DI、I、C组,分别为15mIU/L±4mIU/L;64mIU/L±9mIU/L;49mIU/L±14mIU/L)。免疫组化显示胰岛素受体广泛分布于肺组织内,A、AI、ADI组肺泡腔内、血管及支气管周围浸润染色阳性细胞明显增多。糖尿病组胰岛素受体mRNA表达显著高于非糖尿病组(0.2588±0.0809vs0.0896±0.0308,P=0.00)。结论低剂量胰岛素可明显增强大鼠气道变应性炎症反应。炎症状态下机体胰岛素分泌增多。气道变应性炎症反应时肺组织内浸润的炎症细胞表面及支气管壁分泌细胞胰岛素受体增多。
Objective To reveal the possible mechanism underlying the inverse relationship between IDDM and asthma and the role of insulin and insulin receptor in allergic airway inflammation. Methods Diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin. Rats were sensitized by subcutaneous injection of ovalbumin （OVA） and challenged with an aerosolized solution of 1% OVA for 20 min 14 days after sensitization to provoke allergic airway inflammation. Sixty-four male Spragne-Dawley rats were divided into 8 groups ： group A （asthma） , group D （ diabetes ） , group I （ insulin treated ） , group AD （asthma＋diabetes ）, group AI （asthma＋insulin treated ）, group DI （diabetes＋insulin treated） , group ADI （ asthma ＋ diabetes ＋ insulin treated ） , and group C （ control ）. Blood glucose measurements, total and differential leukocyte counts and serum insulin measurements were carried out. Bronchoalveolar lavage （BAL） were performed, total and differential cell counts were determined. Hematoxylin-eosin stained paraffin section of lung tissue was examined to observe the histological changes. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR. Results All groups of diabetes had higher blood glucose levels than non-diabetes groups. After antigen challenge, the rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. The serum insulin levels were higher in groups ADI, AI and A （ 27 mIU/L ＋ 8 mIU/L, 83 mIU/L ＋ 12 mIU/L, 71 mIU/L＋12 mIU/L respectively ） compared with their respective control group （group DI, I, C, 15 mIU/L±4 mIU/L, 64 mIU/L±9 mIU/L;49 mIU/L±14 mIU/L respectively ）. Immunohistochemistrical staining for insulin receptor revealed a diffused distribution pattern of the receptor in the lung tissue. Positive cells infiltrating in the alveolar spaces, submucosa of bronchus, blood vessels, and bronchial mucosa were increased significantly in groups A, AI and ADI. In groups with induced diabetes the expression of insulin receptor mRNA was elevated compared with that in the non-diabetes groups （ 0. 2588±0. 0809 vs 0. 0896±0. 0308, P=0.00 ）. Conclusion Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion is increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells are increased.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第48期3419-3424,共6页
National Medical Journal of China
基金
国家自然科学基金资助项目(30370610)
关键词
糖尿病
哮喘
胰岛素
受体
气道炎症
Diabetes mellitus
Asthma
Insulin
Insulin receptor
