Chen Chang, Zhang Zongze, Li Zijia, Zhang Fan, Peng Mian, Chen Yingying, Wang Yanlin
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Donghu Road, Wuhan, 430071, Hubei, People's Republic of China.
Mol Biol Rep. 2014 Feb;41(2):809-14. doi: 10.1007/s11033-013-2920-9. Epub 2014 Jan 14.
Mechanical ventilation can cause direct injury to the lungs, a type of injury known as ventilator-induced lung injury (VILI). VILI is associated with up-regulates angiotensinogen and AT1 receptor expression of in the lung. This work explored effects of losartan on VILI in diabetic mice. Ninty-six C57Bl/6 mice were randomly divided into six groups, control group (C group), diabetes group (D group), diabetes mechanical ventilation group (DV group), losartan control group (L + C group), losartan treatment group in diabetic mice (L + D group) and losartan treatment group in mechanical ventilation diabetic mice (L + DV group). Lung W/D, myeloperoxidase (MPO) activity, microvascular permeability, blood-gas analysis, Ang II concentrations and AT-1R protein expression were measured. Compared with D group, DV group increased Ang II concentrations, AT-1R protein expression, W/D ratio, MPO activity, and microvascular permeability. PaO2 were significantly lower in the DV group than D group or control group. Compared with DV group, L + DV group attenuates ventilator-induced lung injury in diabetic mice and prevented the increase Ang II concentrations, AT-1R protein expression and microvascular permeability caused by ventilation in diabetic mice. This study provides in vivo evidence that losartan attenuates microvascular permeability via down-regulates Ang II and AT-1R expression in mechanical ventilator-induced lung injury in diabetic mice.
机械通气可导致肺部直接损伤，这种损伤称为呼吸机诱导的肺损伤（VILI）。VILI与肺中血管紧张素原和AT1受体表达上调有关。这项工作探讨了氯沙坦对糖尿病小鼠VILI的影响。将96只C57Bl/6小鼠随机分为六组，对照组（C组）、糖尿病组（D组）、糖尿病机械通气组（DV组）、氯沙坦对照组（L + C组）、糖尿病小鼠氯沙坦治疗组（L + D组）和机械通气糖尿病小鼠氯沙坦治疗组（L + DV组）。测量肺湿干重比（W/D）、髓过氧化物酶（MPO）活性、微血管通透性、血气分析、血管紧张素II（Ang II）浓度和AT-1R蛋白表达。与D组相比，DV组的Ang II浓度、AT-1R蛋白表达、W/D比值、MPO活性和微血管通透性增加。DV组的动脉血氧分压（PaO2）显著低于D组或对照组。与DV组相比，L + DV组减轻了糖尿病小鼠的呼吸机诱导的肺损伤，并防止了糖尿病小鼠通气引起的Ang II浓度、AT-1R蛋白表达和微血管通透性增加。本研究提供了体内证据，表明氯沙坦通过下调糖尿病小鼠机械通气诱导的肺损伤中的Ang II和AT-1R表达来减轻微血管通透性。
