Hu Yuxin, Ma Zhongsen, Guo Zhimin, Zhao Fenglian, Wang Yuan, Cai Lu, Yang Junling
Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, 130041, China.
Cell Biochem Biophys. 2014 Nov;70(2):1385-91. doi: 10.1007/s12013-014-0068-4.
The objective of this study was to assess the clinical and histopathological relationship between pulmonary fibrosis and type 1 diabetes. We examined clinical pulmonary function parameters and transbronchial lung biopsies to assess associated histopathological changes in 12 type 1 diabetic patients presenting with dyspnea. Lung CT images pulmonary function tests from 12 diabetic patients without dyspnea and from 12 matched normal subjects served as controls. A similar histopathological analysis, including cytokine levels and pro-fibrotic markers, was performed on lung tissues in mice after the induction of experimental diabetes in an attempt to strengthen the link between diabetes and pulmonary fibrosis. Pulmonary function parameters (FVC, FEV1, TLC, and DLco/VA) were significantly reduced in diabetic patients with dyspnea and without dyspnea, compared to controls. Both patient groups also had increased lung CT scores and symptoms compared to normal controls, though the greatest increases were in the diabetic patients with dyspnea. Chronic hyperglycemia induced in mice led to histopathological changes in the lungs that were similar to those found in the human diabetic subjects and included alveoli compression by hyperplastic interstitium infiltrated with inflammatory cells and fibrotic in nature. Two inflammatory related genes, TNF-α and PAI-1, and two fibrosis-related genes, CTGF and fibronectin, demonstrated increased mRNA and protein expression in diabetic mouse lungs. In conclusion, there were significant clinical and histopathological correlations between pulmonary fibrosis and the presence of type 1 diabetes. Diabetes was clinically associated with pulmonary fibrosis and dysfunction in humans, and diabetes induction led to a similar pulmonary fibrosis in an experimental model. These clinical and non-clinical data suggest that diabetes is an independent risk factor for pulmonary fibrosis.
本研究的目的是评估肺纤维化与1型糖尿病之间的临床和组织病理学关系。我们检查了12例出现呼吸困难的1型糖尿病患者的临床肺功能参数和经支气管肺活检，以评估相关的组织病理学变化。来自12例无呼吸困难的糖尿病患者和12例匹配的正常受试者的肺部CT图像及肺功能测试作为对照。在诱导实验性糖尿病后，对小鼠肺组织进行了类似的组织病理学分析，包括细胞因子水平和促纤维化标志物，以试图加强糖尿病与肺纤维化之间的联系。与对照组相比，有呼吸困难和无呼吸困难的糖尿病患者的肺功能参数（FVC、FEV1、TLC和DLco/VA）显著降低。与正常对照组相比，两组患者的肺部CT评分和症状也有所增加，尽管增加最多的是有呼吸困难的糖尿病患者。小鼠中诱导的慢性高血糖导致肺部出现与人类糖尿病受试者相似的组织病理学变化，包括增生性间质压迫肺泡，间质浸润炎性细胞且具有纤维化性质。两个炎症相关基因TNF-α和PAI-1，以及两个纤维化相关基因CTGF和纤连蛋白，在糖尿病小鼠肺中mRNA和蛋白表达均增加。总之，肺纤维化与1型糖尿病的存在之间存在显著的临床和组织病理学相关性。糖尿病在临床上与人类肺纤维化和功能障碍相关，并且在实验模型中诱导糖尿病会导致类似的肺纤维化。这些临床和非临床数据表明，糖尿病是肺纤维化的一个独立危险因素。
