舒芬太尼联合瑞芬太尼静脉麻醉对兔内毒素性急性肺损伤时促炎因子的影响

Effect of intravenous anesthesia combined with sufentanil and remifentanil on the proinflammatory cytokines of rabbits with endotoxin induced acute lung injury

目的:探讨舒芬太尼联合瑞芬太尼静脉麻醉与二者单独使用对兔内毒素性急性肺损伤(ALI)时促炎因子的影响。方法:健康成年雄性新西兰大白兔60只,体质量2.2~2.8 kg,随机分为5组(n=12):对照组(C组)、急性肺损伤组(ALI组)、瑞芬太尼组(RF组)、舒芬太尼组(SF组)、瑞芬太尼+舒芬太尼组(M组)。C组,30 min静脉泵注生理盐水10 mL;ALl组,30 min静脉泵注大肠杆菌脂多糖(LPS)0.7 mg·kg^-1;RF组与SF组先静脉泵注LPS(方法同ALI组)再分别静脉泵注瑞芬太尼0.8μg·kg^-1·min^-1,舒芬太尼0.02μg·kg^-1·min^-1;M组先静脉泵注LPS(方法同ALI)后静脉缓慢推注舒芬太尼1.0μg·kg^-1,3 min后静脉泵注瑞芬太尼0.8μg·kg^-1·min^-1。各组分别于泵注LPS前(T0)、泵注结束即刻(T1)、泵注结束1(T2)、3(T3)、6(T4)h时记录平均动脉血压(MAP)、心率(HR),测定动脉血氧分压(PaO2)、肿瘤坏死因子(TNF)-α及白介素(IL)-1、 IL-6、IL-8的浓度;称量肺组织湿重(W)和干重(D),计算W/D比;观察肺组织病理学结构变化。结果:在T0~T1时段,各组各项检测结果均无显著性差异(P>0.05)。在T2~T4时段:与C组比较,ALI组、RF组、SF组和M组的MAP、HR、PaO2均降低(P<0.05),W/D比值、和血浆TNF-α、IL-1、IL-6、IL-8的浓度均升高(P<0.05);与ALI组比较,RF组、SF组和M组PaO2、MAP、HR均升高(P<0.05),肺组织W/D比和血浆TNF-α、IL-1、IL-6、IL-8的浓度降低(P<0.05);M组、RF组和SF组相比较,PaO2、MAP、HR变化以及肺组织W/D比和血浆TNF-α、IL-1、IL-6、IL-8的浓度变化均无显著性差异(P>0.05)。整个实验过程中各组生命体征的稳定性:C组>M组>SF组>RF组>ALI组。肺组织病理学损伤结果表明,RF组、SF组和M组均较ALI组减轻。结论:瑞芬太尼、舒太尼静脉麻醉可使内毒素性急性肺损伤兔血液中TNF-α、IL-1、IL-6、IL-8的浓度降低,从而减轻其肺损伤的程度。二者联合使用与单独使用对炎症因子的影响无显著性差异。

OBJECTIVE To investigate the effects of sufentanil with remifentanil administered by intravenous anesthesia as well as each alone on proinflammatory cytokines in rabbits with endotoxin-induced acute lung injury(ALI). METHODS 60 healthy adult male New Zealand white rabbits weighing from 2.2 to 2.8 kg were randomly divided into 5 groups(n=12);Control group(group C), acute lung injury group(ALI group), remifentanil group(RF group), sufentanil group(SF group), remifentanil with sufentanil group(group M). C group, saline 10 mL was intravenously injected in 30 min;ALI group, E. coli lipopolysaccharide(LPS) 0.7 mg·kg^-1 was intravenously injected within 30 min;RF group and SF group were intravenously injected with LPS(the same method as ALI group) firstly;Then, remifentanil 0.8 μg·kg^-1·min^-1 and sufentanil 0.02 μg·kg^-1·min^-1 were intravenously injected;M group, LPS and sufentanil 1.0 μg·kg-1 were intravenously injected;then, remifentanil 0.8 μg·kg-1·min-1was intravenously injected 3 min later. The mean arterial blood pressure(MAP), heart rate(HR), arterial oxygen pressure(PaO2), tumor necrosis factor(TNF) and concentration of α interleukin IL-1, IL-6, IL-8 were recorded before the injection of LPS(T0),immediately after the injection of LPS(T1), and at 1(T2), 3(T3), and 6(T4) h after LPS injection in each group. Meanwhile, the wet(W) and dry(D) weight of lung tissue were measured, the W/D ratio was calculated and the pathological changes of lung tissue were observed. RESULTS There was no significant difference in the detection results of each group from T0 to T1(P>0.05);During T2-T4 period, compared with group C, MAP, HR, and PaO2 in ALI group, RF group, SF group, and M group were decreased(P<0.05). W/D ratio, and plasma concentrations of TNF-α, IL-1, IL-6, and IL-8 were increased(P<0.05). Compared with group ALI, PaO2, MAP, and HR in RF group, SF group, and M group were increased(P<0.05), and lung tissue W/D ratio and plasma concentrations of TNF-α, IL-1, IL-6, and IL-8 were decreased(P<0.05). Compared with group M, RF group, and SF group, PaO2, MAP, HR changes, and lung tissue W/D ratio and plasma concentrations of TNF-α low, IL-1, IL-6, and IL-8 were not significantly different(P>0.05). The stability of vital signs in each group throughout the experiment: Group C >Group M >Group SF >Group RF>Group ALI. The results of lung injury showed that RF group, SF group and M group were all less than ALI group. CONCLUSION The combination of remifentanil and sufentanil can decrease the levels of TNF-α, IL-1, IL-6 and IL-8 in the blood of endotoxin-induced acute lung injury, so as to the degree of lung injury. There was no significant difference in the effect of inflammatory factors for the combination use of remifentanil and sufentanil compared to use each one alone.