摘要目的 应用肺损伤模型全面研究前列腺素E1脂微球制剂(1ipo-PGEl)对肺损伤的保护效应.方法 应用静脉输注内毒素加大容量控制通气法制备猪肺损伤模型.将16头猪随机均分为给药组及对照组.置人肺动脉导管,监测动脉、混合静脉血气分析;测定基础值及给予内毒素后2、3、4和5 h的血液动力学及肺气体交换参数.用气道阻塞技术描记两组动物的静态压力-容积(P-V)曲线,并利用S形曲线回归公式拟合,P-V曲线以进一步确定和比较其呼吸力学参数.用酶联免疫吸附法(ELISA)检测血清肿瘤坏死因子-α(TNF-α)及白细胞介素-8(IL-8)浓度.结果 实验期间对照组平均动脉压(MAP)及心排血指数(CI)均明显下降(P 均<0.05),给药组血流动力学较稳定.除基础测定外,给药组在各监测时间点所有氧合指标[包括动脉血氧分压(PaO2、氧合指数(PaO2/FiO2)、肺-动脉血氧分压差(A-aDO2)和肺内分流率(Qs/Qt)]的改善均显著优于对照组(P均<O.05).给药组呼吸力学各种指标(包括上、下拐点)亦优于对照组(P 均<0.05).两组血清TNF-α及IL-8浓度虽都升高,但给药组升高程度不如对照组,且随给药时间的延长下降较快(P均<0.05).结论 Lipo-PGE1对肺损伤有确切的保护效应,且对血流动力学有稳定效应.

abstractsObjective To assess the protective effect of prostaglandin E1 liposome (lipo-PGE1) on acute lung injury (ALI) in a porcine model of ALI.Methods The ALI model was reproduced by lipopolysaccharide (LPS) intravenous instillation and high tidal volume ventilation.A total of 16 domestic pigs were randomized to receive lipo-PGE1 (n=8) or placebo (n=8).Parameters of haemodynamics and pulmonary gas exchange were monitored through pulmonary artery catheter and blood gas analysis at baseline and 2,3,4 and 5 hours after LPS instillation.The inflation quasi-static pressure-volume (P-V) curve was obtained by ventilator occlusion technique,and the P-V data sets were fit with sigmoidal equation in order to define and compare the respiratory mechanics in animals of two groups.Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbent assay (ELISA).Results There was a decrease in cardiac index (CI) and mean arterial Pressure (MAP) in control group compared with those in the group who received lipo-PGE1.In the group receiving lipo-PGE1 the parameter of oxygenation,including partial pressure of oxygen in arterial blood (PaO2),oxygenation index (PaO2/FiO2),and alveolar-arterial oxygen difference (A-aDO2) were significantly improved (all P<0.05) and pulmonary shunt (Qs/Qt) associated with lung injury was also significantly reduced (P<O.05) compared with control group.The respiratory mechanics (including lower and upper inflection point) in the group given lipo-PGE1 were better than those of control group (all P<0.05).Plasma levels of TNF-α and IL-β were found to rise in both groups,but the rise in TNF-α and IL-8 in the group in which lipo-PGE1 was given were lower with shorter period compared with control group (all P<0.05). Conclusion Intravenous delivery of lipo-PGE1 significantly attenuate ALI caused by LPS instillation and high tidal ventilation,and it also shows beneficial effects on haemodynamics.