异丙酚早期给药对内毒素休克大鼠急性肺损伤的保护作用

Protective effects of prophylactic propofol on the lungs against acute injury induced by endotoxin in rats

目的 观察不同时点给予异丙酚对脂多糖(LPS)致内毒素休克大鼠急性肺损伤(ALI)的保护作用及机制。方法静脉注射LPS 8 mg·kg-1复制内毒素致ALI模型,雄性Wistar大鼠76只随机分为5组:对照组(A组,n=8)、LPS组(B组,n=17)、异丙酚给药组(C-E组,n=17),C组、D组和E组分别于LPS注入前1 h、LPS注入即刻、LPS注入后1 h、静脉注射异丙酚5 mg·kg-1,继以10mg·kg-1·h-1持续泵注。从注入LPS至实验结束,历时5 h。持续监测平均动脉压(MAP),测定支气管肺泡灌洗液(BALF)中蛋白(BALFpro)、一氧化氮(NO)、肿瘤坏死因子(TNF-α)、肺组织湿/干重比、肺通透指数(PPI)、肺组织中硝基酪氨酸(NT)表达、NT的Western Blot、肺组织中诱生型一氧化氮合酶mRNA表达及大鼠死亡率。结果 与基础值比较,B组、C组、D组、E组在注入LPS后3、5 h MAP降低(P<0.05),与B组比较,C组、D组注入LPS后5 h MAP降低(P<0.05)。与A组比较,B组、D组、E组PPI、W/D、BALFpro及BALF中TNF-α、NO均升高(P<0.01),C组 W/D、BALFpro及BALF中TNF-α、NO升高(P<0.01);与B组比较,C组、D组PPI、W/D、BALFpro及BALF中TNF-α、NO均降低(P<0.05或0.01),E组W/D、BALFpro及。BALF中NO降低(P<0.05)。与B组比较,A组NT微弱表达,B组表达明显增强,C组、D组、E组表达减弱,以C组最明?

Objective To investigate the effects of propofol administered before, with or after lipopolysaccharide (LPS) on the acute lung injury (ALI) induced by IPS in rats. Methods Seventy-six male Wistar rats weighing 250-290 g were randomly divided into 5 groups : (A) control group received only normal saline (n = 8); (B) LPS group received LPS 8 mg·kg-1 iv (n = 17); (C, D, E) propofol group-Ⅰ,Ⅱ, Ⅲreceived propofol (a bolus of 5 mg·kg-1 followed by infusion at 10 mg·kg-1·h-1) 1 h before (group C, propofol - Ⅰ , n = 17) , simultaneously with (group D, propofol-Ⅱ, n=17) or 1h after LPS administration (group E, propofol-Ⅲ , n = 17) . The animals were observed for 5h after LPS administration for MAP monitoring and mortality and then killed. The lungs were immediately removed for determination of expressions of nitrotyrosine protein and iNOS mRNA, wet / dry lung weight ratio and pulmonary permeability index (PPI). The lungs were also lavaged. The bronchoalveolar lavage fluid (BALE) was collected for measurement of TNF-α, NO and protein contents. Results In group C and D propofol given before and simultaneously with LPS significantly inhibited the increase in nitrotyrosine protein and iNOS expression induced by LPS, improved MAP, reduced 5h mortality rate, decreased PPI and protein, NO and TNF-αcontents in BALF compared with group B (P < 0.01 or 0.05) . In group E the protective effects of propofol was significantly weaker. Conclusion The study showed that propofol administered before LPS provides best protective effects on the lungs against acute injury induced by LPS.