控氧灌注对体外循环犬肺损伤的影响及机制探讨

摘要

目的 探讨控氧灌注(OCR)对体外循环犬肺缺血再灌注损伤的影响及机制.方法 将14只健康犬随机分为OCR及IR组各7只.两组均开胸建立体外循环,经过60 min升主动脉阻断和90 min再灌注.OCR组主动脉开放瞬间FiO2为40％,随后每5 min依次上调10％,最后达80％并保持至实验结束；IR组主动脉开放后再灌注全程FiO2保持80％不变.开胸后(T1)、主动脉开放后25 min(T2)、90 min(T3)分别留取血液标本及肺标本,检测血清IL-6和TNF-α含量,肺组织核转录因子κB( NF-κB)蛋白表达、髓过氧化物酶(MPO)活性、丙二醛(MDA)含量、肺组织干湿重；光镜下观察肺组织病理变化.结果 OCR组动脉血氧分压于主动脉开放后各时点均低于IR组(P＜0.05)；T2和T3时OCR组肺组织NF-κB蛋白表达显著低于IR组(P均＜0.05),肺组织MPO活性、MDA,血IL-6和TNF-α水平明显低于IR组.OCR组肺组织干湿重比在T2和T3时点明显高于IR组,病理改变较轻.结论 控氧灌注可减轻体外循环肺损伤；其机制可能为降低肺组织NF-κB蛋白表达及减轻局部炎症反应.%Objective To investigate the effects and mechanism of oxygen controlled reperfusion (OCR) on the lung ischemia-reperfusion injury (IR) in canine. Methods Fourteen canines were randomized into IR group and OCR group with 7 in each. Both groups received 60 mins aortic clamping followed by 90 mins reperfusion after thoracotomy and CPB establishment. In OCR group, the animals received 40% FiO2 immediately after aortic declamping, then FiO2 increased 10% every five minutes till reaching 80% , which last to the end of CPB; In IR group, the animals received steady 80% FiO2 during reperfusion stage . Lung tissue and blood samples were collected at Tl ( after sternotomy) , T2 (25 mins after aortic declamping ) and T3 (90 mins after aortic declamping). The level of IL-6 and TNF-α in serum, the dry / wet weight (D/W) of the lung tissues, the level of NF-kB expression, myeloperoxidase ( MPO ) activity, malonyldialdehyde (MDA ) and pathological changes of the lung tissues were examined. Results Arterial oxygen pressure (PaO2) was significantly lower in the OCR group at each time point after aortic declamping (P<0. 05). At T2 and T3 point, lung tissue NF-kB expression(P <0.05) , MPO activity and MDA in OCR group were significantly lower than those in IR group. Serous IL-6 and TNF-αin OCR group were also lower than those in IR group. Lung tissue D/W at T2 and T3 point was higher and minor pathological changes in OCR group. Conclusion OCR can against lung injury during cardiopulmonary bypass in canine, the mechanism maybe relate with the reduction of NF-kB expression and local inflammation.