氨基胍对全肝血流阻断再灌注大鼠肺损伤的影响

Effects of aminoguanidine on the lung injury induced by the total hepatic ischemia-reperfusion in rats

目的:探讨氨基胍(AG)对全肝血流阻断再灌注大鼠肺损伤的影响。方法:阻断肝门及肝上、肝下下腔静脉20 m in建立大鼠全肝血流阻断再灌注模型。将90只大鼠随机均分成假手术组(A组)、全肝血流阻断组(B组)和全肝血流阻断加氨基胍治疗组(C组),每组再根据观察时间段的不同随机均分成3个亚组。A,B两组按1mL/kg从股静脉注射生理盐水,C组注射AG 20 mg/kg(溶于1 mL/kg生理盐水中)。观察各组全肝血流阻断20 m in(T0)、再灌注4 h(T1)门静脉血一氧化氮(NO)、内毒素(ET)、肿瘤坏死因子(TNF-α)浓度,大鼠48 h生存率,大鼠肺组织湿干质量比及电镜下组织结构变化。结果:与A组比较,B,C两组T0,T1门静脉血NO,ET,TNF-α及肺湿干质量比明显升高(P<0.05或P<0.01),但C组明显低于B组(P<0.05);B,C两组大鼠48 h存活率降低,但C组明显高于B组(P<0.05);B,C两组肺组织均存在病理改变,但C组明显轻于B组。结论:氨基胍具有保护全肝血流阻断再灌注大鼠肺组织的作用。

Objective To investigate the effects of aminoguanidine on the lung injury induced by the total hepatic ischemia-reperfusion in rats. Methods The total hepatic ischemia-reperfusion model was built after blocking of the hepatic porta, suprahepatic and infrahepatic vena cava. Ninety Sprague-Dawley rats were assigned randomly into 3 groups： Sham operation group （Group A, n = 30） ; total hepatic ischemia group （ Group B, n = 30） ; and aminoguanidine treatment group （ Group C, n = 30）. Each group was subdivided randomly into 3 subgroups （n = 10） according to different time phases： 20 minutes after the total hepatic vascular exclusion （ T0 ）, 4 hours after the reperfusion （ T1）, and 48 hours after the survival. Group A and Group B were intravenously injected with normal saline （ 1 mL/kg） while Group C was injected with aminoguanidine （20 mg/kg） dissolved in normal saline （1 mL/kg） 10 minutes before the open of the abdomin. The levels of portal blood nitric oxide （ NO）, endotoxin （ ET）, tumor necrosis factor-α （TNF-α） at To and Tl were detected; 48 hours survival rates and the lung wet/dry weight ratio were counted ; and the histological changes of the lung tissues were observed. Results Compared with Group A, the levels of portal vein NO, ET, and TNF-α at T0 and T1 in Group B and Group C were significantly higher （ P 〈 0. 05 or P 〈 0. 01 ）. But those indexes of Group C were lower than those of Group B （ P 〈 0. 05 ）. The 48-hour survival rate in Group C was higher than that in Group B （P 〈 0. 05 ）. The lung wet/dry weight ratio in Group C was lower than in Group B （ P 〈 0. 05 ） and the histological change of Group C was slighter than that in Group B. Conclusion Aminoguanidine has the protective effects on the lungs against the total hepatic ischemia-reperfusion induced injury.