3种急性肺损伤兔模型的比较

Comparison of 3 rabbit models of acute lung injury

目的:比较3种常用的急性肺损伤(ALI)动物模型造模效果。方法:24只健康成年日本大白兔随机分为3组,每组8只,气管插管后,行机械通气。盐酸造模组(HCL组):经气管导管给予0.1mol/L的盐酸3ml/kg;脂多糖造模组(LPS组):通过中心静脉30min内缓慢滴注LPS1mg/kg;肠系膜上动脉缺血再灌注复合腹腔内放置粪便组(SMA组):钳闭肠系膜上动脉30min,期间腹腔内放置肠内容物(1ml/kg)与血(1ml/kg)的混合物。连续描记平均动脉压(MAP)和心率(HR)的变化;检测基础(T0)及造模后1,2,4,6,8h(T1,T2,T4,T6和T8)的动脉血气和血清内IL-1β的浓度;实验结束测定血清内肺表面活性物质相关蛋白A(SP-A)的浓度。结果:PaO2在T1,T2时点,HCL组较LPS组和SMA组明显降低(P<0.01);在T4时点3组无统计学差异;在T6,T8时点HCL组和SMA组较LPS组明显降低(P<0.01)。MAP和HR在HCL组和LPS组内各时点无统计学差异;SMA组内与T0时点相比较,T4～T8时点的MAP较低(P<0.01)、HR较快(P<0.01)。IL-1β浓度在HCL组各时点无统计学差异,而LPS组和SMA组则随着时间的发展,IL-1β的浓度逐渐变化;血清内SP-A的浓度,SMA组明显高于另外两组(P<0.01)。结论:与盐酸支气管滴注造模和脂多糖中心静脉滴注造模相比,肠系膜上动脉缺血再灌注复合腹膜内放置粪便法,既可持续保持PaO2水平较低,也可保证血清内炎性因子浓度较高,更可能会发展为急性呼吸窘迫综合征(ARDS)。

Objective：To compare 3 widely used rabbit models of acute lung injury （ALl）. Methods：A total of 24 Japanese white rabbits were randomly assigned （n=8 in each group） to receive bronchoalveolar instillation of hydrochloric acid （HCl,3 mg/kg） in HCl group, central vein infusion of lipopolysaccharide （LPS, 1 mg/kg） in LPS group,and intraperitoneal placement of a compound of feces （1 ml/kg） and blood （1 ml/kg） during superior mesenteric artery occlusion for 30 minutes in SMA group. The rabbits were anesthetized and mechanically ventilated. The mean arterial pressure （MAP） and heart rate （HR） were continuously monitored during the experiment. Blood samples were obtained for blood gas analysis,and the concentrations of interleukin-1β （IL-1β） were measured at the baseline （T0） and 1,2,4,6,and 8 hours （T1,T2,T4,T6,T8） after ALI. The level of surfactant protein A （SP-A） in serum was detected at the end of the experiment. Results： PaO2 was significantly lower in HCl group than in other 2 groups at T1 and T2 （P 〈 0.01 ）;no between-group differences in PaO2 were found at T4;PaO2 was significantly lower in HCl and SMA groups than in LPS group at T6 and T8 （P〈 0.01）. No significant differences in MAP and HR were found between HCl and LPS groups at all time points, In SMA group, the MAP decreased significantly and the HR increased significantly from T4 to T8 （P〈 0.01 ）,compared with those at T0. The concentration of IL-1β did not change in HCl group,but it significantly changed in other 2 groups. The level of SP-A in the serum was significantly higher in SMA group than in other 2 groups. Conclusion： Compared with bronchoalveolar instillation of hydrochloric acid and central vein infusion of LPS, the ALI model estabhshed by intraperitoneal placement of a compound of feces and blood during superior mesenteric artery occlusion is more valuable in the study of ALI.