Wösten-van Asperen R M, Lutter R, Haitsma J J, Merkus M P, van Woensel J B, van der Loos C M, Florquin S, Lachmann B, Bos A P
Paediatric Intensive Care Dept, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands.
Eur Respir J. 2008 Feb;31(2):363-71. doi: 10.1183/09031936.00060207. Epub 2007 Oct 24.
Ventilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation. Rats were ventilated for 4 h with low- or high-pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Nonventilated animals served as controls. ACE activity, Ang II and bradykinin levels, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labelling)-positive cells. Bronchoalveolar lavage fluid ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high-pressure amplitude group as compared with the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in the latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril. The current authors conclude that inflammation and apoptosis in ventilator-induced lung injury is, at least in part, due to angiotensin-converting enzyme-mediated angiotensin II production.
呼吸机诱导的肺损伤以炎症和细胞凋亡为特征，但其潜在机制尚不清楚。本研究提出血管紧张素转换酶（ACE）通过血管紧张素II（Ang II）和/或缓激肽在急性肺损伤中发挥作用。作者评估了ACE以及（如果存在的话）Ang II和/或缓激肽是否参与机械通气引起的炎症和细胞凋亡。在不存在或存在ACE抑制剂卡托普利的情况下，将大鼠分别以低压或高压幅度通气4小时。未通气的动物作为对照。测定了ACE活性、Ang II和缓激肽水平以及炎症参数（总蛋白、巨噬细胞炎性蛋白-2和白细胞介素-6）。通过活化的半胱天冬酶-3数量和TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）阳性细胞数量评估细胞凋亡。与对照组相比，高压幅度组支气管肺泡灌洗液中的ACE活性、总蛋白水平、炎症参数和凋亡细胞数量均增加。卡托普利阻断ACE活性可减轻后一组的炎症和细胞凋亡。阻断Ang II受体也得到了类似结果，但阻断缓激肽受体并未减弱卡托普利的抗炎和抗凋亡作用。作者得出结论，呼吸机诱导的肺损伤中的炎症和细胞凋亡至少部分归因于血管紧张素转换酶介导的血管紧张素II生成。
