不同剂量内皮素A受体阻滞剂对急性肺损伤氧合及换气功能的影响

Impact of inhalation of endothelin-A receptor antagonist on acute lung injury in dogs

目的观察内皮素A(ET-A)受体阻滞剂(LU-135252)对急性肺损伤(ALI)肺换气功能及炎性变化的影响。方法建立24只ALI模型犬,随机均分为3mg/kgLU-135252吸入1组(L1组)、0.5mg/kgLU-135252吸入2组(L2组)和对照组(C组)。于肺灌洗前(T0)、灌洗后即刻(T1)、灌洗后1h合并雾化治疗30min(T2)、灌洗后2h(T3)、3h(T4)、4h(T5)分别监测三组循环功能、血气和血浆内皮素-1(ET-1)水平;取肺组织观察肺炎性变化。结果三组T2～T5时心输出量(CO)比T0时明显降低(P<0.05);L2组平均肺动脉压(MPAP)T3～T5时明显低于L1组和C组(P<0.01);与L1组和C组比较,L2组动脉氧分压(PaO2)、动脉氧饱和度(SaO2)、混合静脉血氧饱和度(SvO2)于T2～T5时显著升高(P<0.01),于T4、T5时动脉二氧化碳分压(PaCO2)和肺内分流值(Qs/Qt)明显降低(P<0.01);与T0时比较,三组ET-1水平在ALI后均升高(P<0.05或P<0.01),但L2组ET-1水平在T2～T5时低于L1组和C组(P<0.05)。三组均有肺损伤改变,L2组肺间质炎和肺间质出血度低于L1组和C组(P<0.05)。结论吸入0.5mg/kgLU-135252可减轻炎性改变,改善ALI的氧合和换气功能。

Objective To observe the impact of inhalation of LU-135252（endothelin-A（ET-A） receptor antagonist） on oxygenation and inflammation in experimental dogs with acute lung injury （ALI）. Methods After ALI model was established, 24 dogs were divided into three groups with 6 dogs each. The dogs in group L1 inhaled LU-135252 3 mg/kg in 10 ml of normal saline, in group L2 LU-135252 0. 5 mg/kg,and in group C normal saline as the controls. The hemodynamics, blood gas and plasma ET-1 levels were monitored before lavage（T0）, at onset of ALI（T1 ）, at 1 h（T2）,2 h（T3）, 3 h（T4 ）,and 4 h（T5 ） after lavage. After the experiment, lung tissues were taken and observed under microscope. Results Compared with T0 ,CO was reduced at T2 ,T3 ,T4 and T5 in three groups（P〈 0.05）. Mean pulmonary artery pressure（MPAP） of L2 group was significantly lower than that of group L1 and C at T3 ,T4 and T5 （P〈0. 01）. Compared with group L1 and C,PaO2 ,SaO2 and mixed venous oxygen saturation（SvO2 ） of group L2 were significantly higher at T2, T3, T4,T5 （P〈0. 01） and PaCO2 and intrapulmonary shunt fraction（Qs/Qt） of group L2 were significantly lower at T4, T5 （P〈0. 01）. The plasma levels of ET-1 were higher after ALI than those at T0 in three groups（P〈0. 05）,which were lower in group L2 than those in group L1 and C at T2, T3, T4 and T5 （P〈0. 05）. Histologic analysis revealed lung injury in three groups, but interstitial inflammation and interstitial bleeding of group L2 were significantly less than those of group L1 and C（P〈0. 05）. Conclusion Inhalation of LU-135252 0. 5 mg/kg may attenuate the inflammation response and impeove oxygenation and gas exchange of clogs with ALI.