乌司他丁对呼吸机相关性肺损伤大鼠肺组织影响的研究

Study of effects on lung with ulinastatin in rat of ventilation-induced lung injury

目的探讨乌司他丁(Uti)对机械通气大鼠肺组织的影响。方法40只健康SD大鼠随机分为5组,每组8只:自主呼吸组(C)、大潮气量通气组(M)以及通气前应用乌司他丁1万u/kg组(U1)、5万u/kg组(U5)和10万u/kg组(U10)。除C组外均给予容量控制性通气4h(参数设置:VT=30mL/kg;RR=40次/min;I/E=1∶3;FiO2=21%)。通气中监测动脉血气。实验结束收集支气管肺泡灌洗液(BALF)和肺组织标本,分别测定肺湿/干重比(W/D),BALF中总蛋白含量、白细胞总数和分类;并对肺组织行病理学观察。结果①M组大鼠通气中PaO2逐渐下降,4h后较基础值差异有显著性(P<0.05)。同C组相比,肺W/D比值和BALF中白细胞总数和蛋白含量明显升高。②通气前预先应用Uti各组PaO2降低明显减缓。同M组比较,肺W/D比值和BALF中白细胞计数和蛋白含量明显减少,其中U1组的变化不明显,而U5和U10组与M组比较差异有显著性(P<0.05)。结论Uti可以通过抑制肺组织中性粒细胞的募集和活化,减少肺血管内蛋白渗出,保护机械通气大鼠肺组织,且保护作用似呈剂量依赖性。

[Objective] To explore the effects of tdinastatin （Uti） for lung in healthy rat with ventilation induced lung injury. [Method] Forty healthy SD rats were randomly divided into five groups, with eight animals in each： sham group（C）; large tidal volume ventilation group （M）; pretreatment of Uti with doses of 10 ku/kg （U1）, 50 ku/kg （U5）, 100 ku/kg（U10）. Except C group, others received ventilation for 4 h （parameter setting： Vt=30 ml/kg, RR= 40 breaths/min, I/E=1：3, FiO2=21%）. After ventilated for 4 h, the histological changes of the lungs were observed under light microscope. The concentrations of proteins, the counts of the total leukocyte and the differential counts in BALF were determined. [Result]（1）With 4 h ventilated, PaO2 in the M group were significantly reduced compared with baseline values. Compared with C group, the lung W/D ratio; the level of proteins; the total numbers of leukocries and leukocyte differential counts in BALF were great elevated. （2）Prior treatment with Uti lessened all above index in different degrees. There were no statistical differences between the U1 group and the M group, but the differences between the U5 and U10 group with M group were distinct. [Conclusion] Uti could attenuate the lung injury from high tidal volume ventilation through suppressing the recruitment and activation of neutrophil and reducing the proteinum effusion for pneumoangiogram. The effects of lung in rat are dose dependent.