瑞芬太尼对兔内毒素性急性肺损伤的影响

Effects of remifentanil on lipopolysaccharide-induced acute lung injury in rabbits

目的探讨瑞芬太尼对兔内毒素性急性肺损伤（ALI）的影响。方法健康成年雄性新西兰大白兔30只，体重2．5～3．5kg，随机分为5组（n=6）：对照组（C组）、ALI组、低剂量瑞芬太尼组（LR组）、中剂量瑞芬太尼组（MR组）和高剂量瑞芬太尼组（HR组）。C组经30Bin静脉输注生理盐水10ml；ALI组经30min静脉输注大肠杆菌内毒素（LPS）0．5mg／kg；LR组、MR组和HR组分别静脉输注瑞芬太尼0．2、0．4和0．8ug·kg^-1·min^-1至处死，输注15min时开始给予LPS，方法同ALI组。于LPS输注前即刻（T0）、输注结束后1、2．5、5．5h时记录平均动脉血压（MAP）、心率（HR）和气道峰压（Ppeak），测定动脉血氧分压（PaO2）和血浆细胞间粘附分子1（ICAM-1）浓度，称量肺组织湿重（W）和干重（D），计算W／D比，并在光镜和电镜下观察肺组织病理学结果。结果与C组比较，ALI组MAP、HR和PaO2降低，W／D比、Ppeak和血浆ICAM-1浓度升高（P〈0．05）；与ALI组比较，LR组、MR组和HR组MAP、HR升高，肺组织W／D比降低,Ppeak和血浆ICAM-1浓度降低，PaO2升高（P〈0．05）；与LR组比较，MR组和HR组MAP、HR、Ppeak、血浆ICAM-1浓度和肺组织W／D比降低，PaO2升高（P〈0．05）；与MR组比较，HR组注肺组织W／D比降低，PaO2升高（P〈0．05）。LR组、MR组和HR组肺组织病理学损伤较ALI组减轻。结论瑞芬太尼可减轻兔内毒素性急性肺损伤，且呈剂量依赖性，其机制可能与抑制ICAM-1的表达有关。

Objective To investigate the effects of remifentanil on lipopolysaccharide （LPS）-induced acute lung injury （ALl） in rabbits. Methods Thirty healthy male New Zealand white rabbits weighing 2.5-3.5 kg were randomly divided into 5 groups （ n = 6 each） ： group Ⅰ control （group C） ; group Ⅱ ALI; group Ⅲ , Ⅳ, Ⅴ low, median and high dose RF ＋ LPS （group LR, MR, HR）. The animals were anesthetized with intravenous 3% pentobarbital sodium 30 mg/kg, tracheostomized and mechanically ventilated. The carotid artery and jugular vein were cannulated for MAP and HR monitoring, blood sampling, and fluid and drug administration. LPS 0.5 mg/kg in 10 ml of normal saline （NS） was infused over 30 rain in group Ⅱ- Ⅴ . Remifentanil 0.2, 0.4 or 0.8 ug·kg^-·min^-1 was infused starting from 15 min before LPS administration until the death of the animals. MAP, HR, peak airway pressure （Ppook）, PaO2 and plasma intercellular adhesion molecule 1 （ICAM-1） concentration were measured innnediately before LPS infusion （TO , baseline） and at 1, 2.5 and 5.5 h after the end of LPS infusion. The animals were killed and the lungs were immediately removed for microscopic examination and determination of W/D lung weight ratio. Results MAP, HR and PaO2 were significantly decreased while W/D ratio and Ppeak were significantly increased after iv LPS inlusion as compared with control group. LPS significantly increased plasma iCAM-1 concentration and damaged the structure of lung tissue. Remifentanil infusion significantly attenuated the LPS-induced changes in a dose-dependent manner. Conclusion RF has protective effect against LPS-induced ALI and inhibition of ICAM-1 expression is involved in the mechanism.