Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Laboratory of Cardiovascular Surgery and Physiopathology of Circulation (LIM-11), Heart Institute (InCor), Medicine School, University of Sao Paulo, Brazil.
Pulm Pharmacol Ther. 2018 Apr;49:54-59. doi: 10.1016/j.pupt.2018.01.005. Epub 2018 Jan 11.
Acute lung injury (ALI) is a common complication after intestinal ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress syndrome (ARDS). We have previously demonstrated that females are protected against lung damage induced by intestinal I/R through an estrogen mediated mechanism.
To investigate the effect of obesity on ALI induced by intestinal I/R in female mice.
C57Bl/6 female mice were fed with a standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R injury was induced by a 45 min occlusion of the mesenteric artery followed by 2 and 24 h of reperfusion.
Significant increase in lung myeloperoxidase expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24 h of reperfusion. Furthermore, HFD mice presented a significant increase in lung eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SD mice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24 h of reperfusion, accompanied by a significant increase in the expression of inducible NO in the lung tissue and a significant decrease in arterial oxygen saturation at 24 h of reperfusion relative to SD mice.
Obesity predisposes female mice to increased pulmonary oedema and deterioration in gas exchange, which is accompanied by an increase in iNOS expression in the lung.
探讨肥胖对雌性小鼠肠缺血再灌注(I/R)诱导的急性肺损伤(ALI)的影响。
C57Bl/6 雌性小鼠分别用标准低脂饮食(SD)或高脂饮食(HFD)喂养 9 周。通过肠系膜动脉闭塞 45 分钟,再灌注 2 和 24 小时来诱导肠 I/R 损伤。
在再灌注 2 和 24 小时时,SD 和 HFD 小鼠的肺髓过氧化物酶(MPO)表达和中性粒细胞数量显著增加。此外,与 SD 小鼠相比,HFD 小鼠的肺嗜酸性过氧化物酶(EPO)表达和嗜酸性粒细胞数量显著增加。HFD 小鼠在再灌注 2 和 24 小时时的肺湿/干重比显著升高,同时肺组织中诱导型一氧化氮合酶(iNOS)的表达显著增加,再灌注 24 小时时的动脉血氧饱和度显著降低。
肥胖使雌性小鼠更容易发生肺水肿和气体交换恶化,同时肺组织中 iNOS 的表达增加。