胰岛素对内毒素所致的急性肺损伤的防治作用  

Preventive and therapeutic effect of insulin on lipopolysaccharide-induced acute lung injury in rabbits

作　　者：梁韶军[1] 刘曼玲[2] 李志超[2] 张博[2] 崔晓岗[1] 卢军杰[1] 李斌[1] 

机构地区：[1]西安市中心医院麻醉科,陕西西安710003 [2]第四军医大学病理与病理生理学教研室,陕西西安710032

出　　处：《心脏杂志》2009年第4期475-479,共5页Chinese Heart Journal

基　　金：西安市科技计划项目基金资助(GG06155)

摘　　要：目的观察胰岛素(insulin,ISL)对内毒素(LPS)引起的兔急性肺损伤(ALI)的预防与治疗作用,并初步探讨其作用机制。方法将新西兰兔随机分为生理盐水(NS)对照组、LPS组、ISL+LPS组及LPS+ISL组,气管内滴注LPS建立兔ALI模型。采用微量注射泵经兔耳缘静脉滴注不同的液体,NS组和LPS组:滴注生理盐水;ISL+LPS组:滴注ISL混合液(ISL+葡萄糖+KCl)0.5h后,再于气管内滴注LPS;LPS+ISL组:先经气管内滴注LPS0.5h后,再滴注ISL混合液。滴注时间持续4h,期间监测兔平均颈总动脉压(mCAP)、血糖及血钾的变化。实验结束后处死实验动物,取肺组织观察形态学改变、测定肺湿/干质量的比值(W/D),并分别用亚硝酸盐显色法和硫代巴比妥法测定肺组织匀浆中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量及活性。结果LPS组兔随时间mCAP逐渐下降,实验结束时下降至(8.09±1.12)kPa,与NS组相比差异显著(P<0.05)。应用ISL预防和治疗后,mCAP下降的趋势缓慢,基本保持平稳,与LPS组相比有显著性差异(P<0.05)。LPS组兔的血糖随时间延长逐渐增高,实验结束时达峰值至(12.8±5.6)mmol/L,与NS组相比差异显著(P<0.05)。应用ISL预防和治疗后,兔的血糖随时间变化不明显,与LPS组相比差异明显(P<0.05)。实验期间各组兔的血钾基本保持平稳。形态学观察表明,LPS组肺组织水肿有点、片状出血,大量炎性细胞浸润,肺泡间隔显著增厚,肺泡腔变窄,结构消失。ISL+LPS组及LPS+ISL组的肺损伤明显减轻,肺组织结构均趋于正常;肺泡腔及支气管腔炎细胞及渗出物明显减少。与NS组相比,LPS组兔的肺W/D明显增加(P<0.05),肺组织匀浆中SOD的活性显著降低(P<0.05),MDA的含量显著升高(P<0.05);而ISL+LPS组及LPS+ISL组兔的肺W/D明显减少(P<0.05),肺组织匀浆中SOD的活性显著增加(P<0.05),MDA的含量显著降低(P<0.05)。结论ISL对LPS所致兔ALI具有预防与治疗的作用,其作用可能与抑制肺组织中的氧化�AIM： To observe the role of insulin in the prevention and treatment of lipopolysaccharide （LPS）-induced acute lung injury （ALI） in rabbits and to further explore the underlying mechanism by which insulin exerts protective effects on LPS-induced ALI. METHODS： New Zealand white rabbits were divided randomly into four groups ： saline control group, LPS group, insulin ＋ LPS group and LPS ＋ insulin group. The animal model of ALI was established by intratraeheal administration of LPS 0.5 mg/ （ml·kg）. Microinjection pump was used to inject solution through ear-edge vein. NS group and LPS group received normal saline for 4 hours. Insulin ＋ LPS group received insulin mixed liquor 0. 5 hour before intratracheal administration of instilled LPS. LPS ＋ insulin group received insulin mixed liquor 0. 5 hour after intratracheal administration of instilled LPS. The insulin mixed liquor was given continuously for 4 hours. During that period, the mean carotid arterial pressure （mCAP）, the glucose of venous blood and the K ＋ concentration of arterial blood were monitored. After experiment, the histological changes of lungs were observed and the left lung wet-to-dry （W/D） weight ratios were evaluated. SOD and MDA in lung homogenate were also measured. RESULITS： reCAP declined persistently （8.09 ± 1.12） kPa and the contents of glucose of venous blood persistently ascended （ 12. 8± 5.6） mmol/L in LPS group. But insulin kept reCAP at higher levels （P 〈 0.05）. Histological studied showed that there were congestion, edema and the sequestration of inflammatory cells in lung tissues in LPS group, but lung injury was significantly alleviated in insulin ＋ LPS and LPS ＋ insulin groups. The W/D and the content of MDA highly increased and the activity of SOD decreased （P 〈 0. 05 ） in LPS group. Insulin inhibited all the increased parameters and upgraded the activity of SOD （P 〈 0. 05）. CONCLUSION： Insulin prevents and relieves LPS-induced rabbit ALI, which may be related wi

关 键 词：急性肺损伤 脂多糖 胰岛素 超氧化物歧化酶 丙二醛 

分 类 号：R977.15[医药卫生—药品]