西维来司钠对体外循环中犬肺损伤的保护作用

Protective effects of sivelestat against acute lung injury during cardiopulmonary bypass in dogs

目的:探讨西维来司钠对体外循环(CPB)中犬肺损伤的保护作用.方法:随机将健康成年犬分为对照组(C组,n=6)和西维来司钠组(S组,n=6).建立犬CPB模型,两组均在转机前(T1),阻断升主动脉15 m in(T2),45 m in(T3),开放30 m in(T4),60 m in(T5)取肺组织和静脉血.静脉血离心后测血浆弹性蛋白酶(NE)含量,取肺组织做肺组织细胞间黏附分子-1(ICAM-1)的免疫组化染色并进行图像分析及光镜学检查.肺组织匀浆离心取上清液测丙二醛(MDA)含量.结果:(1)CPB后,两组动物肺组织ICAM-1表达逐渐增强,与S组相比,C组肺组织ICAM-1表达强烈,其平均灰度值明显大于S组(P<0.01);肺组织结构的破坏严重;(2)CPB后,两组动物各时点血浆NE含量及肺组织匀浆MDA含量均显著高于CPB前(P<0.01).同时各时间点组间比较,S组CPB后各时点血浆NE含量、肺组织匀浆MDA含量均低于C组(P<0.01,P<0.05).结论:西维来司钠可通过抑制血浆NE的活性,使肺组织间ICAM-1的表达减弱,减少氧自由基的生成,对CPB中犬肺损伤有较好的防治作用.

AIM： To study the protective effects of sivelestat against acute lung injury during cardiopulmonary bypass （CPB）. METHODS： Twelve adult mongrel healthy dogs were randomly divided into control （ n = 6） and sivelestat groups （ n = 6）. CPB models were established. Plasma neutrophil elastase （NE） and malondialdehyde （MDA） in lung tissues were detected before CPB （T1 ）, 15 min （T2） and 45 min （T3 ） after cross-clamping of aorta, and 30 min （T4 ）, 60 min （T5 ） after aortic unclamping. Specimens of lung tissues were taken for optical microscopic examination and the intercellular adhesion molecule-1 （ ICAM-1 ） of lung tissues was examined with immunohistochemical technique and image analysis. RESULTS： （ 1 ） After CPB, the ICAM-1 expression in the lung tissues increased gradually in both groups and was more significant in control group when compared with sivelestat group, and the average grey value of ICAM-1 in lung tissue was higher significantly in control group than that in sivelestat group （ P 〈0.01 ）. Damage of structure in the lung tissues was more severe in control group than that in sivelestat group. （2） Plasma levels of NE and MDA in lung tissues after CPB were higher than those before CPB in both groups （ P 〈 0.01 ）. However, they were significantly lower in sivelestat group than that in control group at all the time points （P 〈0.01, P 〈0.05）. CONCLUSION： Sivelestat inhibits the level of plasma NE and the expression of ICAM-1, minimizes the production of free radical in the lung tissues and may prevent lung injury during CPB.