First Department of Critical Care and Pulmonary Services, Evangelismos Hospital, National and Kapodistrian University of Athens, Greece.
Department of Clinical Biochemistry, Attikon Hospital, National and Kapodistrian University of Athens, Greece.
Int J Surg. 2018 Jul;55:156-161. doi: 10.1016/j.ijsu.2018.05.735. Epub 2018 May 31.
Lung ischemia-reperfusion injury after thoracoabdominal aortic occlusion represents a major complication, which increases morbidity and mortality. In the present study we hypothesized that lazaroid U-74389G intravenous administration protects from lung ischemia-reperfusion injury through lipid peroxidation inhibition.
A total of 24 pigs were randomized in three groups. Group I (n = 8) underwent sham operation, group II (n = 8) underwent thoracoabdominal aortic occlusion for 45min and received placebo and group III (n = 8) received 3 doses of lazaroid (3 mg/kg) 60 and 30min before thoracoabdominal aortic occlusion and at 30min during thoracoabdominal aortic occlusion (duration 45min). Aortic occlusion was performed with aortic balloon-catheters under fluoroscopic guidance. All animals were sacrificed at the 7 t h postoperative day and lung specimens were harvested for molecular analysis.
mRNA levels of leukotrienes LB4 (LTB4R2), LC4 (LTC4S) and nitric oxide synthase (NOS) isoforms including iNOS, nNOS and eNOS were determined with real-time RT-qPCR. Nitric oxide can either induce (iNOS) or inhibit (nNOS and eNOS) lipid peroxidation based on its specific isoform origin. Group III showed significantly reduced mRNA levels of LTB4R2 (-63.7%), LTC4S (-35.9%) and iNOS (-60.2%) when compared with group II (P < 0.05, for all). The mRNA levels of nNOS was significantly increased (+37.4%), while eNOS was slightly increased (+2.1%) in group III when compared with group II (P < 0.05 and P = 0.467 respectively).
Lazaroid U-74389G may represent an effective pharmacologic intervention in reducing lung ischemia-reperfusion injury following thoracoabdominal aortic occlusion.
胸主动脉阻断后肺缺血再灌注损伤是一种主要并发症，增加了发病率和死亡率。本研究假设拉扎罗伊德 U-74389G 静脉给药通过抑制脂质过氧化来保护肺缺血再灌注损伤。
共 24 头猪随机分为三组。I 组（n=8）行假手术，II 组（n=8）行胸主动脉阻断 45min 并给予安慰剂，III 组（n=8）在胸主动脉阻断前 60min 和 30min 及胸主动脉阻断期间 30min 给予 3 剂拉扎罗伊德（3mg/kg）。在透视引导下用主动脉球囊导管行主动脉阻断。所有动物均于术后第 7 天行心剖检，采集肺标本进行分子分析。
采用实时 RT-qPCR 测定白细胞三烯 LB4（LTB4R2）、LC4（LTC4S）和一氧化氮合酶（NOS）同工型包括诱导型 iNOS、nNOS 和内皮型 eNOS 的 mRNA 水平。一氧化氮可以根据其特定同工型的来源诱导（iNOS）或抑制（nNOS 和 eNOS）脂质过氧化。与 II 组相比，III 组 LTB4R2（-63.7%）、LTC4S（-35.9%）和 iNOS（-60.2%）的 mRNA 水平显著降低（均 P<0.05）。与 II 组相比，III 组 nNOS 的 mRNA 水平显著升高（+37.4%），而 eNOS 的 mRNA 水平略有升高（+2.1%）（均 P<0.05 和 P=0.467）。
拉扎罗伊德 U-74389G 可能是一种有效的药物干预手段，可减少胸主动脉阻断后肺缺血再灌注损伤。
