帕瑞昔布预处理对肺缺血再灌注损伤大鼠的保护作用及机制

Protective effect of parecoxib preconditioning on lung ischemia-reperfusion injury in rats

目的探讨帕瑞昔布预处理对肺缺血再灌注损伤(LIRI)大鼠的保护作用及机制。方法将32只雄性SD大鼠随机分为4组(n=8):假手术组(S组)、缺血再灌注组(I组)、帕瑞昔布组(P组)及锌原卟啉组(Z组)。S组仅游离不阻断左肺门,其他三组通过阻断左肺门建立单侧LIRI模型。P组在阻断左肺门前15 min经股静脉给予帕瑞昔布10 mg/kg,Z组在缺血前24 h经腹腔注射锌原卟啉20 mg/kg,S组、I组经股静脉注射等体积生理盐水。检测阻断前5 min(T0)及再灌注后120 min(T1)各组动脉血气指标,计算氧合指数(OI)和肺泡动脉血氧分压差(PA-a O2);计算肺组织湿干重比(W/D);观察肺组织病理改变;用RT-PCR、Western blotting法分别检测肺组织中血红素加氧酶1(HO-1)mRNA及蛋白表达。结果 T1时,与S组比较,I组、P组及Z组中OI低、PA-a O2高(P均<0.05),且I组、Z组OI、PA-a O2变化更明显(P均<0.05)。与S组比较,其余三组W/D值高(P均<0.05),且I组、Z组W/D值较P组高(P均<0.05)。肺缺血再灌注后I组、P组及Z组肺组织损伤明显,但P组较其他两组轻。与S组比较,I组、P组及Z组中HO-1 mRNA、蛋白表达高(P均<0.05),且P组最高(P均<0.05),I组与Z组比较差异无统计学意义(P均>0.05)。结论帕瑞昔布预处理可改善LIRI后大鼠肺氧合功能,减轻肺损伤;其作用机制与上调肺组织中HO-1表达有关。

Objective To investigate the protective effect of parecoxib preconditioning on lung ischemia-reperfusion injury（ LIRI） in rats and its mechanism. Methods Thirty-two male SD rats were randomly divided into four groups（ n =8） ： sham operation group（ group S）,ischemia-reperfusion group（ group I）,parecoxib group（ group P）,and zinc protoporphyrin group（ group Z）. Unilateral LIRI model was established by blocking the hilum of the left lung. In the group I,the hilum of the left lung was dissociated and blocked. In the group P,15 minutes before the left lung hilum was blocked,parecoxib 10 mg/kg was injected via the femoral vein. In the group Z,24 hours before ischemia,Zinc protoporphyrin 20 mg/kg was injected intraperitoneally. In addition,an equal volume of saline was injected via the femoral vein in the group S and group I. Arterial blood gas was measured at 5 min before hilar was blocked（ T0） and 120 min（ T1） after reperfusion. Oxygenation index（ OI） and alveolar arterial oxygen pressure difference（ PA-a O2） were calculated; lung wet/dry weight ratio（ W/D ratio） was calculated. The pathological changes of lung tissues were observed. The expression of heme oxygenase 1（ HO-1） mRNA and protein in the lung tissues were detected by RT-PCR and Western blotting. Results At T1,compared with group S,OI decreased and PA-a O2 increased in the group I,group P,and group Z（ both P〈0. 05）,and those were more significant in the group I and group Z（ both P〈0. 05）. Compared with group S,the lung W/D ratio was higher in the other three groups（ P〈0. 05）,and lung W/D ratio in the group I and group Z was higher than that in the group P（ P〈0. 05）. After lung ischemia-reperfusion,the lung tissues of group I,group P,and group Z were significantly damaged,but the group P was less than the other two groups. Compared with group S,the expression of HO-1 mRNA and protein in the group I,group P,and group Z increased,with the highest increase in group P（ all P〈0. 05）; there was no significant difference between group I and group Z（ P〉0. 05） Conclusion Parecoxib pretreatment can improve lung oxygenation and reduce pulmonary edema after LIRI in rats by up-regulating the HO-1 expression in the lung tissues.