肠缺血后处理抑制大鼠肠缺血再灌注所致的急性肺损伤

Intestinal ischemic postconditioning attenuates acute lung injury induced by intestinal ischemia/reperfusion in rats

目的:研究肠缺血后处理对大鼠肠缺血再灌注(I/R)所致急性肺损伤的影响及机制。方法:40只SD大鼠随机分为5组(n=8):假手术组(对照组),仅分离而不阻断肠系膜上动脉(SMA);肠I/R损伤组,阻断SMA1 h后再灌注1 h;缺血预处理(IPC)组,在长时间阻断SMA前预先阻断SMA10 min然后开放10 min;缺血后处理(IPo)组,在阻断SMA1 h后连续进行3个循环的开放SMA30 s/阻断SMA30 s(总时间为3 min),然后开放1 h;延迟后处理(delay)组,在再灌注3 min(IPo的总时间)后行3个循环的30 s缺血/30 s再灌注的缺血后处理,余同IPo组。监测平均动脉压(MAP),于再灌注1 h后取肺组织光镜下观察肺形态学的变化,检测血清及支气管肺泡灌洗液蛋白含量并计算肺通透性指数,称肺湿重及干重并计算肺含水率,检测肺组织丙二醛(MDA)的含量,超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)的活性,检测血清TNF-α及IL-6的浓度。结果:缺血后处理与预处理都能显著改善肺损伤,显著降低肺通透性指数及肺含水率,同时降低血浆TNF-α与IL-6的浓度、肺组织MDA含量及MPO活性,升高SOD活性。后处理被延迟3min后,其肺保护作用消失,且不能显著改变上述指标。结论:缺血后处理与预处理都具有抗肠I/R后肺损伤的作用,可能与其清除氧自由基、抑制中性粒细胞的肺内聚集及炎症细胞因子的释放有关;而且,再灌注早期后处理对肺的保护作用最关键。

AIM： Previous study has shown that brief period of repetitive superior mesenteric artery （SMA） occlusion and repeffusion applied at the onset of reperfusion, ischemic postconditioning （IPo） , attenuates intestinal injury after intestinal ischemia/reperfusion （I/R）. This study tested the hypothesis that IPo would attenuate intestinal I/R -induced acute lung injury which is comparable to ischemic preconditioning （IPC） and the brief period of postconditioning applied at the onset of reperfusion is critical to pulmonary protection by IPo. METHODS ： Rat intestinal I/R injury was produced by clamping SMA for 60 min followed by 60 min of reperfusion. The rats were randomly allocated into one of five groups based upon the intervention （n = 8） ： sham operation （sham） ： sham surgical preparation including isolation of the SMA without occlusion was performed; injury： there was no intervention either before or after SMA occlusion; ischemia preconditioning （IPC） ： the SMA was occluded for 10 min followed by 10 min of reperfusion before prolonged occlusion; ischemia postconditioning （IPo） ： 3 cycles of 30 s reperfusion -30 s reocclusion were imposed immediately upon reperfusion （3 min total intervention） ; delayed postconditioning （delay） ： clamping was completely released for full reperfusion for 3 min （ the duration of the IPo algorithm）, after which 3 cycles of 30 s occlusion and reperfusion were applied. RESULTS ： Histological results showed severe damages in rat lungs in the injury group evidenced by increased lung wet/dry weight ratio and pulmonary permeability index, which was accompanied by increases in the levels of plasma TNF - α and IL - 6, the pulmonary malondialdehyde （MDA）, and the pulmonary myeloperoxidase （MPO） activity, and a decrease in superoxide dismutase （SOD） activity. IPo, not delayed IPo, significantly attenuated lung injury and improved the above variables, which was comparable to IPC. CONCLUSION ： IPo at onset of reperfusion reduces acute lung injury induced by intestinal I/R, which may be mediated, in part, by inhibiting oxidant generation, filtration of neutrophils and releases of proinflammatory mediators. The early period of reperfusion in the rat model is critical to pulmonary protection by IPo. IPo may improve outcome in clinical conditions associated with intestinal I/R.