Effect of losartan on mechanical ventilation-induced lung injury in diabetic mice
10.3760/cma.j.issn.0254-1416.2012.10.021
- VernacularTitle:洛沙坦对糖尿病小鼠机械通气相关肺损伤的影响
- Author:
Chang CHEN
;
Zijia LI
;
Juan LI
;
Mian PENG
;
Yingying CHEN
;
Yanlin WANG
;
Zongze ZHANG
- Publication Type:Journal Article
- Keywords:
Losartan;
Diabetes mellitus;
Respiration,artificial;
Respiratory distress syndrome,adult
- From:
Chinese Journal of Anesthesiology
2012;(10):1235-1238
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of losartan on mechanical ventilation-induced lung injury in diabetic mice.Methods Forty-eight female SPF C57/BL6 nice,aged 10-12 months,weighing 20-25 g,were randomly assigned into 3 groups (n =16 each):control group (group C).,diabetes + mechanical ventilation (group DM) and losartan group (group L).Diabetes mellitus was induced by intraperitoneal streptozotocin 150 mg/kg and confirmed by blood glucose level ＞ 16 mmol/L in groups DM and L.Diabetic mice were mechanically ventilated (FiO250％,VT 15 ml/kg,RR 70 bpm,PEEP 2 cm H2O) for4 h.Losartan 30 mg/kg was injected intraperitoneally 30 min before ventilation in group L.Eight mice from each group were chosen at 4 of ventilation and arterial blood samples were obtained for detection of PaO2.The animals were then sacrificed and the lungs were removed for determination of W/D lung weight ratio,myeloperoxidase (MPO) activity,pulmonary microvascular permeability,angiotensin Ⅱ (Ang Ⅱ) receptor AT1 mRNA expression (by RT-PCR),Ang Ⅱ content and nuclear factor kappa B (NF-κB) p65 expression (by Western blot).Results Compared with group C,PaO2 was significantly decreased,while W/D lung weight ratio,MPO activity,pulmonary microvascular permeability and Ang Ⅱ content were significantly increased,and the expression of AT1 mRNA and NF-κB p65 was up-regulated in groups DM and L (P ＜ 0.05).PaO2 was significantly higher,and W/D lung weight ratio,MPO activity,pulmonary microvascular permeability,Ang Ⅱ content and the expression of AT1 mRNA and NF-κB p65 were significantly lower in group L than in group DM (P ＜ 0.05).Conclusion Losartan can reduce mechanical ventilation-induced lung injury in diabetic mice through inhibiting AT1 receptor and Ang Ⅱ levels and improving pulmonary microvascular permeability and inhibiting NF-κB activation.
