南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (12): 1739-.

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氯沙坦降低小鼠呼吸机相关性肺损伤及抑制肺组织内小窝蛋白-1及NOX4的表达

凌旭光,娄安妮,李洋,杨仁强,宁佐伟,李旭   

  • 出版日期:2015-12-20 发布日期:2015-12-20

Losartan regulates oxidative stress via caveolin-1 and NOX4 in mice with ventilatorinduced
lung injury

  • Online:2015-12-20 Published:2015-12-20

摘要: 目的利用呼吸机过度通气建立小鼠机械性肺损伤模型,以血管紧张素II受体抑制剂氯沙坦进行干预,探讨氯沙坦对机械
通气性肺损伤小鼠肺内小窝蛋白-1及氧化应激相关蛋白的调节。方法36只雄性C57小鼠随机分为对照组、机械通气组、单纯
药物对照组和治疗组,建模完成后分别检测各组小鼠急性肺损伤情况以及相关蛋白的表达和相互作用。结果机械通气组小鼠
肺损伤Smith评分3.3,明显高于对照组(0.4)和单纯药物对照组(0.3),治疗组Smith评分2.3,较机械通气组明显降低(P<0.05);
机械通气组小鼠肺组织内小窝蛋白-1 和NOX4 蛋白表达明显高于对照组及单纯药物对照组(P<0.05),荧光共染可见小窝蛋
白-1及NOX4发生荧光重合,治疗组小鼠肺组织内上述蛋白表达较机械通气组明显降低(P<0.05),荧光共染提示小窝蛋白-1及
NOX4荧光重合区域较机械通气组减少。结论在机械通气诱导的小鼠急性肺损伤模型中,氯沙坦可缓解机械通气诱导的肺损
伤并抑制小窝蛋白-1及NOX4的表达及相互趋近作用。

Abstract: Objective To investigate the effect of losartan in regulating oxidative stress and the underlying mechanism in mice
with ventilator-induced lung injury. Methods Thirty-six male C57 mice were randomly divided into control group, losartan
treatment group, mechanical ventilation model group, and ventilation plus losartan treatment group. After the corresponding
treatments, the lung injuries in each group were examined and the expressions of caveolin-1 and NOX4 in the lung tissues were
detected. Results The mean Smith score of lung injury was significantly higher in mechanical ventilation model group (3.3)
than in the control group (0.4), and losartan treatment group (0.3); the mean score was significantly lowered in ventilation
plus losartan treatment group (2.3) compared with that in the model group (P<0.05). The expressions of caveolin-1 and NOX4
were significantly higher in the model group than in the control and losartan treatment groups (P<0.05) but was obviously
lowered after losartan treatment (P<0.05). Co-expression of caveolin-1 and NOX4 in the lungs was observed in the model
group, and was significantly decreased after losartan treatment. Conclusions Losartan can alleviate ventilator-induced lung
injury in mice and inhibit the expression of caveolin-1 and NOX4 and their interaction in the lungs.