米力农对兔早期急性肺损伤TNF-α、IL-1β及IL-10的影响

目的:观察米力农对兔早期急性肺损伤炎性因子TNF-α、IL-1β及抗炎介质IL-10表达的影响,探讨米力农对肺损伤保护机制。方法:将18只家兔麻醉后气管切开行机械通气,随机均分为正常对照组(A组)、急性肺损伤(ALI)模型组(B组)和治疗组(C组)。B、C组采用内毒素滴入气管内复制急性肺损伤(ALI)模型,C组予以米力农50μg/kg静注后以5μg·kg-1·min-1持续输注治疗120 min,A、B组予以输注生理盐水。在基础状态(T1)、建模后0 min (T2)、120 min (T3)时,监测平均动脉压(MAP)和平均肺动脉压(mPAP);采集血标本检测血清TNF-α、IL-1β及IL-10并行动脉血气分析。动物处死后测肺湿/干重比及支气管肺泡灌洗液(BALF)中性粒细胞(PMN)百分比,并观察肺组织形态学变化。结果:与B组比较,C组PaO₂提高,mPAP显著下降(P<0.01),通气功能改善;TNF-α、IL-1β显著下降,IL-10明显上升,BALF中PMN显著减少(P<0.01)。结论:米力农能改善肺通气功能,减轻肺损伤,其作用机制可能是通过增加IL-10的生成,抑制TNF-α和IL-1β的释放,调节炎症/抗炎介质的平衡。

Effects of milrinone on TNF-α,IL-1 and IL-10 expression during acute lung injury in rabbits

Objective：To observe the effects of milrinone on the expression of TNF-α ,IL-1 β and IL-10 during acute lung injury（ALI） in rabbits. Methods： Eighteen rabbits were anesthetized with tracheotomy, and then ventilated mechanically. The animals were randomly allocated into three groups ： group A（ normal control, n = 6 ） , group B （ endotoxin control, n = 6 ） and group C （ treatment group, n = 6 ）. Group B and C were induced into ALI by eodotoxin. Group C were treated by intravenous milrinone at 5 μg · kg^-1 · min^ -1 after a bolus 50 μg/kg;group B and C received normal saline intravenously. The mean systemic arterial pressure （MAP） and mean pulmonary arterial pressure （mPAP） were recorded at the time of baseline （ T1 ） , after modeling 0 （ T2 ） , and 120 min （ T3 ）. The levels of TNF-α, IL-β and IL-10 in serum were detected, and arterial blood gas analysis was made at the same time. Polymorphonuclear neutrophils （PMN） （%） in bronchoalveolar lavage fluid（BALI：） and lung wet-to-dry weight ratio （W/D）were determined after the animals were sacrificed. And lung specimens were obtained to observe the histological changes. Results：Compared with group B,the PaO2 in group C increased and mPAP decreased significantly （P 〈 0.01 ） , and the ventilation function improved. After treatment, the concentrations of TNF-α and IL-1β in serum decreased significantly ,while the concentrations of IL-10 in serum were significantly enhanced（ P 〈0.01 ）. And PMN（ % ） in the BALF decreased significantly （P 〈 0.01 ）. Conclusions： Milrinone could improve the pulmonary gas exchange and attenuate endotoxin-ioduced ALI. The mechanism of the effects may be that milrinone could regulate the imbalance between inflammatory and anti-inflammatory mediators by enhancing the generation of IL-10 and refraining the release of IL-1 β and TNF-α.