Department of Nursing, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
Resuscitation. 2011 Jun;82(6):760-6. doi: 10.1016/j.resuscitation.2011.02.010. Epub 2011 Mar 12.
Haemorrhagic shock and subsequent resuscitation induce acute lung injury. We elucidated whether bilateral lower limb ischemic pre-conditioning (IP) could mitigate lung injury in haemorrhagic shock/resuscitation rats. The role of heme oxygenase-1 (HO-1) was also elucidated.
Adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus IP, or HS plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Sham groups were employed simultaneously. For pre-conditioning, 3 cycles of limb IP (10 min ischemia followed by 10 min reperfusion) were performed immediately before haemorrhagic shock. Haemorrhagic shock (mean arterial pressure: 40-45 mmHg) was induced by blood drawing and maintained for 120 min. SnPP was injected 5 min before resuscitation. Shed blood/saline mixtures were re-infused to achieve resuscitation. After monitoring for another 8h, rats were sacrificed. Arterial blood gas and alveolar-arterial oxygen difference (lung function index), histology, polymorphonuclear leukocytes/alveoli ratio (leukocyte infiltration index), wet/dry weight ratio (water content index), inflammatory molecules (e.g., chemokine, cytokine, prostaglandin E(2)), and malondialdehyde (lipid peroxidation index) assays were preformed.
Haemorrhagic shock/resuscitation induced significant lung function alterations and significant increases in leukocyte infiltration, water content, inflammation, and lipid peroxidation in lungs. Histological analysis confirmed that haemorrhagic shock/resuscitation caused marked lung injury. Limb IP significantly mitigated the adverse effects of haemorrhagic shock/resuscitation. Moreover, the protective effects of limb IP were reversed by SnPP.
Limb IP mitigates lung injury in haemorrhagic shock/resuscitation rats. The mechanisms may involve HO-1.
失血性休克及随后的复苏可导致急性肺损伤。本研究旨在阐明双侧下肢缺血预处理（IP）是否可以减轻失血性休克/复苏大鼠的肺损伤，并探讨血红素加氧酶-1（HO-1）的作用。
成年雄性大鼠随机分为失血性休克/复苏（HS）组、HS 加 IP 组和 HS 加 IP 加 HO-1 抑制剂锌原卟啉（SnPP）组（每组 12 只），同时设立假手术组。预处理时，在进行失血性休克前立即进行 3 个周期的肢体 IP（10min 缺血后再灌注 10min）。通过抽血将平均动脉压维持在 40-45mmHg 诱导失血性休克 120min。SnPP 在复苏前 5min 注射。将抽出的血液/盐水混合物回输以实现复苏。监测 8h 后处死大鼠。检测动脉血气和肺泡-动脉氧差（肺功能指数）、组织学、多形核白细胞/肺泡比值（白细胞浸润指数）、湿/干重比（水含量指数）、炎症分子（如趋化因子、细胞因子、前列腺素 E2）和丙二醛（脂质过氧化指数）。
失血性休克/复苏导致大鼠肺功能明显改变，白细胞浸润、水含量、炎症和脂质过氧化明显增加。组织学分析证实失血性休克/复苏导致了明显的肺损伤。肢体 IP 显著减轻了失血性休克/复苏的不良影响。此外，SnPP 逆转了肢体 IP 的保护作用。
肢体 IP 减轻失血性休克/复苏大鼠的肺损伤。其机制可能与 HO-1 有关。
