氧控制性再灌注抗犬体外循环肺缺血再灌注早期损伤过程中高迁移族蛋白1的表达  

Expression of high mobility group box 1 in the lung protection of oxygen controlled reperfusion against early ischemia-reperfusion injury with cardiopulmonary bypass in canines

作　　者：荣健[1] 叶升[2] 吴钟凯[3] 陈光献[3] 梁孟亚[3] 刘海[3] 黄伟明[1] 王治平[3] 

机构地区：[1]中山大学附属第一医院麻醉科,广州510000 [2]中山大学附属第一医院肿瘤科,广州510000 [3]中山大学附属第一医院心外科,广州510000

出　　处：《中华生物医学工程杂志》2010年第3期195-200,共6页Chinese Journal of Biomedical Engineering

基　　金：基金项目：国家杰出青年科学基金（30525020）

摘　　要：目的探讨氧控制性再灌注抗犬体外循环肺缺血再灌注早期损伤过程中高迁移族蛋白1（HMGBl）的表达。方法健康犬14只按完全随机法分为对照组（n=7）和实验组（n=7），均进行体外循环肺缺血再灌注。对照组全程吸入氧浓度（FiO2）80％；实验组在主动脉开放即刻调整FiO2至40％，随后每5min依次上渊10％，最后达80％，其余时段均维持FiO280％。观察2组犬在麻醉后、主动脉开放前、主动脉开放后5、10、15、20、25min以及停机前动脉血氧分压（PaO2）的变化。在开胸后即刻（T1）、主动脉开放25min（T2）、主动脉开放90min（T3）分别留取血液标本及肺组织标本，检测肺组织HMGBl及NF—κB的表达，酶联免疫吸附法（ELISA）检测血清IL-6和TNF-α含量；检测肺组织湿干质量比及肺组织髓过氧化物酶（MPO）活性、丙二醛（MDA）含量；观察肺组织病理学变化。结果实验组PaO2在主动脉开放后5、10、15、20min均显著低于对照组（均P〈0．05）。与对照组比较，在T2和T3时点实验组HMGBlmRNA表达（T2：0．9260±0．0139比1．0496±0．0306；T3：0．8325±0．0154比0．9894±0．0144，均P〈0．05）和蛋白表达（T2：0．4345±0．0748比0．5512±0．0474；T3：0．4490±0．0541比0．5455±0．0406，均P〈0．05）均降低。实验组肺组织NF—κB蛋白表达在T2和T3时点低于对照组（均P〈0．05）。实验组血清IL-6和TNF—α含量在T2和T3时点低于对照组（均P〈0．05）。实验组肺组织湿干质量比、MPO活性、MDA含量在T2和T3时点均低于对照组（均P〈0．05）。实验组肺损伤评分在T2和T3时点均低于对照组[T2：（2．0±0．7）分比（3．8±0．5）分；T3：（2．6±0．6）分比（4．2±0．8）分，均P〈0．05]。结论氧控制性再灌注对体外循环肺缺血再灌注早期损伤具有保护作用，其机制可能与下调HMGBl表达有关。Objective To observe the expression of high mobility group box 1 （HMGB1）in the lung protection of oxygen controlled reperfusion against isehemia-reperfusion （I/R） with cardiopulmonary bypass （CPB） in canine. Methods Fourteen healthy canines were randomly divided into two groups： control group （n=7） and test group （n=7） , and received CPB. The animals in the control group received 80% FiO2 throughout the whole procedure, whereas those in the test group received 40% immediately at the declamping of aorta, and an additional 10% every 5 rain later until 80% FiO2 was reached. Other procedures were the same with control group. Arterial oxygen partial pressure （PaO2） was recorded after anesthesia was completed, before and at 5, 10, 15, 20, 25 min after sternotomy, and before withdrawal of CPB. HMGB1 expression by RT-PCR and Western blot, NF-KB expression by Western blot, IL-6 and TNF-α by ELISA were analyzed just after sternotomy（T1 ）, 25 min after declamping（T2） and 90 min after declamping（T3）. At the same time points, malondialdehyde, myeloperoxidase activity, wet/dry mass （Mw/MD） and tissue pathology were analyzed. Results PaO2 was significantly lower in the test group than that in the control group at 5, 10, 15 and 20 min after aortic declamping （all P〈0.05）. Compared with the control group at T2 and T3, the test group was found to have lower levels in I-IMGB1 mRNA and protein expressions （T2：0.926 0± 0.013 9 vs 1.049 6±0.030 6;T3：0.832 5±0.015 4 vs 0.989 4±0.014 4,both P〈0.05; T2：0.434 5±0.074 8 vs 0.551 2±0.047 4;T3：0.449 0±0.054 1 vs 0.545 5±0.040 6,both P〈0.05）, NF-KB protein expression in the lung tissues, IL- 6 and TNF-α in serum, Mw/MD ratio, MDA level and MPO activity （all P〈0.05）. Pathological scores in test group at T2 and T3 were significantly lower than those in control group （T2：2.0±0.7 vs 3.8±0.5;T3：2.6±0.6 vs 4.2±0.8, both P〈0.05）. Conclusion Oxygen controlled reperfusion possesses lung protection in early st

关 键 词：氧 炎症 再灌注 肺 体外循环 

分 类 号：R563[医药卫生—呼吸系统]