异丙酚对内毒素致大鼠急性肺损伤的保护作用及机制

The Protective Role and Mechanism of Propofol on Acute Lung Injury by Endotoxin in Rats

目的探讨异丙酚对内毒素致大鼠急性肺损伤(ALI)的保护作用及机制。方法Wistar大鼠随机分成3组,每组20只。对照组(C组):股静脉输注生理盐水5mL在1.5h内输注完毕;内毒素(LPS)对照组(L组):经股静脉输注生理盐水3mL1h,然后再输注LPS8mg/kg(溶于2mL生理盐水中),30min内输注完毕;异丙酚处理组(LT组):异丙酚20mg/kg溶于3mL生理盐水中,经股静脉1h内输注,然后输注LPS(方法如上)。6h时取大鼠肺组织标本,HE染色后观察肺组织形态学的变化;检测肺组织湿/干重(W/D)比、肺水含量、血管壁通透性(EB渗出)、肺通透指数(LPI)等指标反映肺损伤程度;检测丙二醛(MDA)、NO、诱导型NO合成酶(iNOS)、超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)的活性来反映氧自由基的代谢;Kaplan-Meier曲线分析4、6、8、10、12h生存率。结果L组W/D比、EB渗出、LPI、MDA、NO、iNOS、MPO显著高于C组、LT组(P﹤0.01),而SOD较LT组明显下降(P﹤0.01)。结论异丙酚增强SOD活性,抑制iNOS、MPO活性,减少了内毒素致ALI后肺部的炎性反应及氧化应激反应,从而减轻了肺损伤程度。

Objective To investigate the protective role and mechanism of propofol on acute lung injury by endotoxin in rats. Methods Sixty Wistar rats were randomly divided into 3 groups with 20 animals in each group. Control group received only normal 5mL saline for 1.5h by femoral vein;L group received endotoxin 8mg/kg i.v. within 30 minutes after infusing 3mL saline for lh. LT group received endotoxin 8mg/kg i.v. within 30 minutes after infusing propofol 20mg/ kg for lh, Ten animals of every group were killed after receiving endotoxin 6 hours. The left lung was removed and inflate with formalin,The lung were fixed overnight,embedded in paraffin,sectioned at 5um,and stained with hematoxylin and eosin. Lung wey/dry weight ratio,lung water content,lung permeability and evans blue leakage were determined. Meanwile,MDA,NO,iNOS,SOD,MPO,were measured. The survival ratio were analysised by Kaplan-Meier curve. Results The W/D ratio,LPI,MDA,NO,iNOS,MPO in L group were significantly higher than that in C and LT group （P〈0.01）. In contrast, SOD decreased in L group. Conclusion The propofol plays a protective action in acute lung injury by endotoxin in rats,the mechanism of this result may be due to inhibit activity of iNOS and MPO.