米力农对兔早期急性肺损伤TNF-α、IL-1β及IL-10的影响

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

    • 摘要: 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。

       

      Abstract: Objective: To observe the effects of milrinone on the expression of TNF-α,IL-1β 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 endotoxin.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-1β 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(BALF) 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-induced 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-1β and TNF-α.

       

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