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胰岛素对内毒素所致的急性肺损伤的防治作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第4期
页码:
475-479
栏目:
基础研究
出版日期:
2009-06-25

文章信息/Info

Title:
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
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
Author(s):
LIANG Shao-jun1 LIU Man-ling2 LI Zhi-chao2 ZHANG Bo2 CUI Xiao-gang1 LU Jun-jie1 LI Bin11
1.Department of Anesthesiology, Central Hospital, Xian 710003, Shaanxi, China; 2.Department of Pathophysiology, Fourth Military Medical University, Xian 710032, Shaanxi, China
关键词:
急性肺损伤脂多糖胰岛素超氧化物歧化酶丙二醛
Keywords:
acute lung injury lipopolysaccharide SOD MDA
分类号:
R977.15
DOI:
-
文献标识码:
A
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)0.5 h后,再于气管内滴注LPS;LPS+ISL组:先经气管内滴注LPS 0.5 h后,再滴注ISL混合液。滴注时间持续4 h,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应激作用有关。
Abstract:
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 intratracheal 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: mCAP 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 mCAP 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 with the inhibition of oxidative stress.

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备注/Memo

备注/Memo:
收稿日期:2008-12-15.基金项目:西安市科技计划项目基金资助(GG06155) 通讯作者:李志超,教授,博士,主要从事呼吸与循环病理生理学研究Email:lizhic@ fmmu.edu.cn 作者简介:梁韶军,主任医师Email:Lhyxach@yahoo.com.cn 共同第一作者:刘曼玲,助教,硕士Email:apple0210vip@yahoo.com.cn
更新日期/Last Update: 2009-06-15