Jiang Jiunn-Song, Wang Leng-Fang, Chou Hsiu-Chu, Chen Chung-Ming
Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, and Department of Biochemistry, College of Medicine, Taipei Medical University, Taiwan.
J Appl Physiol (1985). 2007 Jun;102(6):2098-103. doi: 10.1152/japplphysiol.00514.2006. Epub 2007 Feb 22.
We hypothesized that lung inflammation and parenchymal apoptosis in ventilator-induced lung injury (VILI) are related to ANG II and assessed the ability of the angiotensin-converting enzyme inhibitor captopril to attenuate VILI in rats. Adult male Sprague-Dawley rats were randomized to receive two ventilation strategies for 2 h: 1) tidal volume of 40 ml/kg, respiratory rate of 25 breaths/min, and inspiratory O2 fraction of 0.21 [high-volume, 0 positive end-expiratory pressure (HVZP) group] and 2) injection of captopril (100 mg/kg ip) 30 min before HVZP ventilation (HVZP+CAP group). Another group, which did not receive ventilation, served as the control. Mean arterial pressure was significantly lower in the HVZP+CAP group than in the HVZP group at 2 h of ventilation. Total protein levels were significantly higher in bronchoalveolar lavage fluid (BALF) recovered from HVZP-ventilated rats than from controls. BALF macrophage inflammatory protein-2 and lung ANG II were significantly higher in the HVZP group than in the control and HVZP+CAP groups. Lung ANG II levels correlated positively with BALF protein and macrophage inflammatory protein-2. The number of apoptotic airway and alveolar wall cells was significantly higher in the HVZP and HVZP+CAP groups than in the control group and significantly lower in the HVZP+CAP group than in the HVZP group. These results suggest that the efficiency of captopril to attenuate VILI is related to reduction of inflammatory cytokines and inhibition of apoptosis and indicate that VILI is partly mediated by the local angiotensin system.
我们推测，机械通气诱导的肺损伤（VILI）中的肺部炎症和实质细胞凋亡与血管紧张素II（ANG II）有关，并评估了血管紧张素转换酶抑制剂卡托普利减轻大鼠VILI的能力。成年雄性Sprague-Dawley大鼠被随机分为两组，接受两种通气策略，持续2小时：1）潮气量为40 ml/kg，呼吸频率为25次/分钟，吸入氧分数为0.21 [高容量、零呼气末正压（HVZP）组]；2）在HVZP通气前30分钟注射卡托普利（100 mg/kg，腹腔注射）（HVZP+CAP组）。另一组未接受通气的大鼠作为对照。通气2小时时，HVZP+CAP组的平均动脉压显著低于HVZP组。从HVZP通气的大鼠回收的支气管肺泡灌洗液（BALF）中的总蛋白水平显著高于对照组。HVZP组BALF中的巨噬细胞炎性蛋白-2和肺ANG II显著高于对照组和HVZP+CAP组。肺ANG II水平与BALF蛋白和巨噬细胞炎性蛋白-2呈正相关。HVZP组和HVZP+CAP组气道和肺泡壁凋亡细胞的数量显著高于对照组，且HVZP+CAP组显著低于HVZP组。这些结果表明，卡托普利减轻VILI的效率与炎性细胞因子的减少和凋亡的抑制有关，并表明VILI部分由局部血管紧张素系统介导。
