1,6-二磷酸果糖对犬体外循环中肺缺血-再灌注损伤保护作用的研究

The protective effects of fructose-1,6-diphosphate on lung ischemia-reperfusion during cardiopulmonary bypass in dogs

目的探讨不同剂量1,6-二磷酸果糖(Fructose-1,6-d iphosphatin,FDP)对犬体外循环(Card iop-u lmonary Bypass)肺缺血-再灌注(Ischem ia-reperfusion,IR)损伤的作用效果和可能机制。方法建立犬体外循环IR损伤模型,将18只健康杂种犬随机分为三组:FDP大剂量组,FDP小剂量组,生理盐水对照组,每组各6只。在体外循环转机前(T1),阻断升主动脉30 m in(T2)、45 m in(T3),开放升主动脉45m in(T4),90m in(T5)检测各组肺组织Na+/K+-ATP酶活力、Ca2+/Mg2+-ATP酶活力超氧化物歧化酶(Superoxide d ismutase)活力、黄嘌呤氧化酶(xanth ine oxidase)活力、丙二醛(M alond ialdehyde)含量。体外循环转机前和结束时取右下肺组织测定肺湿/干比(W/D)值。结果(1)生理盐水对照组与FDP小剂量组肺组织比较:上述指标差别无显著性意义(P>0.05)。(2)生理盐水对照组和FDP大剂量组比较,肺组织SOD活力、Na+/K+-ATP酶活力和Ca2+/Mg2+TP酶活力水平均明显降低(P<0.05);肺组织肺湿/干重比值、XOD活力和MDA含量水平均明显增高(P<0.05)。(3)FDP大剂量组和FDP小剂量组比较:肺组织SOD活力、Na+/K+-ATP酶活力和Ca+/Mg2+-ATP酶活力水平均明显增高(P<0.05);肺组织肺湿/干重比值、XOD活力和MDA含量水平均明显降低(P<0.05)。结论(1)犬CPB中持续静滴大剂量1,6-二磷酸果糖(1 300mg/kg)可通过调节细胞ATP酶活力、SOD活力、XOD活力较大程度减轻肺组织缺血-再灌注损伤。(2)犬CPB中持续静滴小剂量1,6-二磷酸果糖(325mg/kg)对肺组织缺血-再灌注损伤无保护作用。

Objective To investigate the effects of different dosage fructose - 1,6 - diphosphate on acute lung injury induced by lung ischemia - reperfusion during cardiopulmonary bypass in dogs and its possible mechanism. Methods After lung IR model during cardiopulmonary bypass in dogs was established, 18 adult mongrel canines （ 12 - 15kg）were randomly divided into 3 groups： large dosage FDP group（ infusion of FDP at a dose of 1300 mg/kg during cardiopulmonary bypass）, small dosage FDP group （infusion of FDP at a dose of 325 mg/kg during cardiopulmonary bypass） ,saline control group（ infusion of saline at a dose of 13ml/kg during cardiopulmonary bypass ）. The superoxide dismutase （SOD） activity, xanthine oxidase （ XOD ） activity, Na ^＋/K^＋ - ATPase activity, Ca^2＋/Mg^2＋ - ATPase activity, the levels of malondialdehyde（MDA） in lung tissue were examined before CPB （ Tl ） ,30min（ T2 ） and 45 min（ T3 ） after cross - clamping of aorta, and 45min（ T4 ） ,90min（ T5 ）. The wet/dry ratio of lung was analyzed at the end of CPB. Results （ 1 ） There was no significant difference between placebo control group and small dosage FDP group in all index（ P 〉 0. 05 ） ; （ 2 ） The activity of Na^＋/K^＋ - ATPase,Ca2^＋Mg^2＋ -ATPase,SOD in lung tissue of the placebo control group were all significantly lower than those of large dosage FDP group （P 〈 0. 05 ）. The wet/dry weight ratio of lung, the levels of MDA and XOD activity in lung tissue of large dosage FDP group were all significantly higher than those of placebo control group （ P 〈 0. 05 ）. （ 3 ） Comparison of variables between large dosage FDP group and small dosage FDP group ： the activity of Na^＋/K^＋ - ATPase ／ Ca^2＋ Mg^2＋ - ATPase, SOD in lung tissue of large dosage FDP group were all significantly higher than those of small dosage FDP group（ P 〈 0. 05 ）. The wet/dry weight ratio of lung tissue, the levels of MDA and XOD activity in lung tissue of large dosage FDP group were all significantly lower than those of small dosage FDP group（P 〈 0. 05 ）. Conclusions These results indicate that through adjusting the activity of SOD, the activity of XOD, the activity of ATPase and M DA of lung tissue, continuously infusion of fructose - 1,6 - diphosphate at a dose of 1300 mg/kg over the ischemia period could evidently attenuate lung ischemia- reperfusion injury,although less dose of fructose- 1,6 -bisphosphate could not lessen it.