肺表面活性物质防治急性呼吸窘迫综合征的实验研究

Pulmonary surfactant in the prevention and treatment of acute respiratory distress syndrome in rats

目的 探讨肺表面活性物质 (pulmonarysurfactant,PS)对内毒素诱发大鼠急性呼吸窘迫综合征 (acuterespiratorydistresssyndrome ,ARDS)的防治作用。方法 4 8只健康雄性SD大鼠 ,手术并给予机械通气后随机分为 6组 :健康对照组 (H组 ) ,ARDS模型组 (M组 ) ,其余动物根据动脉血氧分压(PaO2 ) /FiO2 比值分 2个时期 (PaO2 /FiO2 ≤ 30 0mmHg早期 E、PaO2 /FiO2 ≤ 2 0 0mmHg晚期 L)和所给猪肺PS分 2个剂量 (5 0mg/kg、 10 0mg/kg) ,两两组合成E5 0、E10 0、L 5 0和L10 0 4组。用PS后共观察 6h。结果 M组和L 5 0组的PaO2 和静态胸肺压力 容积 (P -V)曲线肺容积均较H组明显降低 (P <0 0 1) ,L10 0组上述指标明显高于M组 (P <0 0 5 ) ,而E 5 0组和E10 0组PaO2 和P V曲线肺容积均较L10 0组进一步升高(P <0 0 5 ,P <0 0 1) ,E5 0组和E10 0组间上述指标差别不明显。支气管肺泡灌洗液 (BALF)分析示L 5 0组和L10 0组饱和卵磷脂 (DSPC) /总蛋白 (TP)、TP和最小表面张力 (STmin)均较M组改善 (P <0 0 1) ,但STmin仍高于H组 (P <0 0 1) ,E5 0组和E10 0组的BALF测值均明显优于L10 0组 (P <0 0 1) ,且STmin接近H组。结论 早期应用PS疗效明显优于晚期 ,且所需剂量较小 。

Objective To evaluate the prophylactic and therapeutic effects of pulmonary surfactant(PS) on endotoxin induced acute respiratory distress syndrome(ARDS).Methods Forty eight healthy male adult Sprague Dawley rats were surgical operated and mechanically ventilated with 50% oxygen(FiO 2).Eight animals didnt receive endotoxin and served as healthy control group(H).Another 40 animals received 50 mg/kg of endotoxin administered intratracheally to induce ARDS.When arterial blood oxygen(PaO 2)/FiO 2 was ≤300 mm Hg,they were randomly allocated to 5 groups( n =8 each):ARDS model group(M)not receiving PS, immediate (i e early stage)treatment with PS at a dose of 50 mg/kg(E50) or 100 mg/kg(E100) administered intratracheally,later stage(when PaO 2/FiO 2≤200 mm Hg,approximately 2 h later)treated with PS similar to in early stage(L50,L100).Rats were ventilated for another 6h to observe PaO 2 followed by plotting static thorax lung pressure volume (P V)curve and analysis of desaturated phosphatidylcholine (DSPC),total proteins(TP)and minimum surface tension(ST min )of bronchoalveolar lavage fluid(BALF).Results The animals in the M group and the L50 group had decreased PaO 2 and lung volume on the P V curve( all P <0 01),Compared with the H group,whereas those in the L100 group had modest but statistically significant improvement in above parameters(all P <0 05),compared with the M group.Both the E50 group and the E100 group showed further increased PaO 2 and lung volume on the P V curve( P <0 05 or P <0 01),compared with the L100 group,but there were no significant difference between the E50 group and the E100 group in either measurement above.BALF analysis showed the L50 group and the L100 group had increased DSPC/TP,decreased TP and ST min ,compared with the M group( P <0 01),but the STmin were still higher than the H group( P <0 01),the E50 group and the E100 group had further improved DSPC/TP,TP,ST min (all P <0 01),and the STmin were closed to that of H group.Conclusion Exogenous PS is more effective and the needed doseis smallar when it is used at the early stage of ARDS,and can be an method in the prevention and treatment of this disease.[