Ma Yan-liang, He Quan-ying
Department of Pulmonary Medicine, People's Hospital, Peking University, Beijing 100044, China.
Zhonghua Yi Xue Za Zhi. 2005 Dec 21;85(48):3419-24.
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.
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 Sprague-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.
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). Immunohistochemistry 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).
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.
揭示胰岛素依赖型糖尿病（IDDM）与哮喘之间负相关关系的潜在机制，以及胰岛素和胰岛素受体在过敏性气道炎症中的作用。
通过腹腔注射链脲佐菌素诱导大鼠患糖尿病。大鼠经皮下注射卵清蛋白（OVA）致敏，并在致敏14天后用1% OVA雾化溶液激发20分钟以引发过敏性气道炎症。64只雄性Sprague-Dawley大鼠分为8组：A组（哮喘组）、D组（糖尿病组）、I组（胰岛素治疗组）、AD组（哮喘+糖尿病组）、AI组（哮喘+胰岛素治疗组）、DI组（糖尿病+胰岛素治疗组）、ADI组（哮喘+糖尿病+胰岛素治疗组）和C组（对照组）。进行血糖测量、白细胞总数及分类计数以及血清胰岛素测量。进行支气管肺泡灌洗（BAL），测定细胞总数及分类计数。检查苏木精-伊红染色的肺组织石蜡切片以观察组织学变化。采用免疫组织化学方法描述胰岛素受体的分布，并通过逆转录-聚合酶链反应（RT-PCR）测量胰岛素受体mRNA的表达。
所有糖尿病组的血糖水平均高于非糖尿病组。抗原激发后，A组、AI组、ADI组大鼠表现出以嗜酸性粒细胞和中性粒细胞显著升高为特征的气道炎症，AD组仅表现出轻度气道炎症。与各自的对照组（DI组、I组、C组，分别为15 mIU/L±4 mIU/L、64 mIU/L±9 mIU/L；49 mIU/L±14 mIU/L）相比，ADI组、AI组和A组的血清胰岛素水平较高（分别为27 mIU/L±8 mIU/L、83 mIU/L±12 mIU/L、71 mIU/L±12 mIU/L）。胰岛素受体免疫组织化学染色显示该受体在肺组织中呈弥漫分布模式。A组、AI组和ADI组肺泡腔、支气管黏膜下层、血管和支气管黏膜中浸润的阳性细胞显著增加。在诱导糖尿病的组中，胰岛素受体mRNA的表达较非糖尿病组升高（0.2588±0.0809对0.0896±0.0308，P = 0.00）。
低剂量胰岛素给药加重了大鼠对抗原激发的气道炎症。炎症存在时胰岛素分泌增加。在抗原激发的大鼠肺中，浸润性炎症细胞和支气管分泌细胞表面的胰岛素受体增加。
