Hypoxia-induced acute lung injury is aggravated in Streptozotocin diabetic mice
Hypoxia-induced acute lung injury is aggravated in Streptozotocin diabetic mice
复制标题
链脲佐菌素糖尿病小鼠缺氧引起的急性肺损伤加重。
DOI：
10.3109/01902148.2014.983280
复制
发表时间：
2015-04-01
影响因子：
1.7
通讯作者：
Liu, Yu-Jian
中科院分区：
文献类型：
--
作者：
Wang, Lu-Mei;Zhong, Nan-Zhe;Liu, Yu-Jian
目的：低氧血症是许多呼吸系统疾病不可避免的后果，其原因是肺泡通气不足。肺功能障碍是糖尿病的重要临床表现之一，本研究旨在探讨链脲佐菌素（STZ）诱导的糖尿病对缺氧性肺损伤的影响。材料和方法：将小鼠随机分为4组（对照组、缺氧组、糖尿病组、糖尿病+缺氧组）。对照组和I型糖尿病（100 mg/kg STZ治疗）小鼠随后4周，最后暴露于常氧或缺氧（8%O-2）。12 h后取肺组织行病理学检查，并测定白细胞介素（IL）-1 β、IL-6、髓过氧化物酶（MPO）、丙二醛（MDA）、总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）活性和Toll样受体（TLR）4表达。结果：STZ诱导的糖尿病加重了急性缺氧肺组织病理学改变。缺氧使肺组织MDA含量升高，T-AOC和SOD活性降低。STZ诱导的糖尿病小鼠肺组织MDA水平和SOD活性显著升高。缺氧组与缺氧+糖尿病组的氧化指标（MDA）和抗氧化指标（T-AOC和SOD）无显著性差异。另一方面，STZ诱导的糖尿病小鼠呈现肺中性粒细胞浸润、促炎细胞因子（IL-1 β和IL-6）产生以及TLR 4表达的显著增加。虽然单独急性缺氧对肺部炎症标志物没有显著影响，但它显著增加了STZ糖尿病诱导的中性粒细胞浸润，促炎细胞因子产生和肺组织中TLR 4表达。结论：STZ诱导的糖尿病可能通过增强肺组织炎症反应而加重急性缺氧性肺损伤。
Purpose: Hypoxia is an inevitable consequence of many respiratory diseases resulting from inadequate alveolar ventilation. As pulmonary dysfunction is recently recognized as one of the many clinical features associated with diabetes, this study aims to investigate the effect of streptozotocin (STZ)-induced diabetes on hypoxia-induced lung injury. Materials and Methods: Mice were randomly allocated to four groups (Control, Hypoxia, Diabetes, Diabetes+Hypoxia). Control and type I diabetic (100 mg/kg STZ-treated) mice were followed for 4 weeks and finally exposed to normoxia or hypoxia (8% O-2). Twelve hours later, lung tissues were collected for histopathologic examination, and determination of interleukin (IL)-1 beta, IL-6, myeloperoxidase (MPO), malondi-aldehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and Toll-like receptor (TLR) 4 expression. Results: STZ-induced diabetes aggravated histopathological changes in the lung exposed to acute hypoxia. Hypoxia increased lung MDA level but decreased T-AOC and SOD activity. STZ-induced diabetic mice presented significant increases in MDA level and SOD activity in the lung. Moreover, no difference was found in the levels of both oxidant index (MDA) and anti-oxidant indexes (T-AOC and SOD) between "Hypoxia" group and "Hypoxia plus Diabetes" group. On the other hand, STZ-induced diabetic mice presented significant increases in pulmonary neutrophil infiltration, pro-inflammatory cytokines (IL-1 beta and IL-6) production, as well as TLR4 expression. Although acute hypoxia alone had no significant effect on pulmonary inflammatory markers, it profoundly increased STZ-diabetes-induced neutrophil infiltration, pro-inflammatory cytokine production, and TLR4 expression in lung tissues. Conclusions: STZ-induced diabetes may aggravate acute hypoxia-induced lung injury through enhancing pulmonary inflammatory responses.