胰岛素对内毒素所致的急性肺损伤保护作用的研究  

The preventive and therapeutical effect of insulin on ALI induced by LPS in rabbit

作　　者：梁韶军[1] 刘曼玲[2] 李志超[2] 曹义战[3] 崔晓岗[1] 张博[2] 

机构地区：[1]西安市中心医院麻醉科,西安710003 [2]解放军第四军医大学病理生理学教研室 [3]解放军第四军医大学附属唐都医院急诊科,西安710032

出　　处：《中国急救医学》2009年第7期622-626,676,共6页Chinese Journal of Critical Care Medicine

基　　金：西安市科技计划项目基金资助（No.GG06155）

摘　　要：目的观察胰岛素（Insulin）对脂多糖（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，Insulin＋LPS组及LPS＋Insulin组，气管内滴注LPS建立兔急性肺损伤模型。采用微量注射泵经兔耳缘静脉注射液体，NS组和LPS组注射生理盐水，持续4h；Insulin＋LPS组注射胰岛素混合液，0．5h后再于气管内滴注LPS、胰岛素混合液持续4h；LPS＋Insulin组先经气管内滴注LPS，0．5h后再注射胰岛素混合液，持续4h。4．5h后处死实验动物，取肺组织观察形态学改变、测定肺湿／干质量比值（W／D），肺泡灌洗液（BALF）中蛋白含量，肺组织匀浆中TNF—α、IL-6、LDH和MPO的含量。结果形态学观察表明LPS组肺组织水肿，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。Insulin＋LPS组及LPS＋Insulin组肺损伤明显减轻，肺组织结构均趋于正常；肺泡腔及支气管腔炎性细胞及渗出物明显减少。LPS组肺W／D与NS组相比明显增加（P〈0．05），BALF中蛋白含量显著增加（P〈0．05），肺组织匀浆中TNF-α、IL-6、LDH和MPO的含量显著增加（P〈0．05）；而给予胰岛素预防及治疗后，肺W／D、BALF中蛋白含量、肺组织匀浆中TNF—α、IL-6、LDH和MPO的含量与LPS组相比均明显减少（P〈0．05）。结论Insulin能够防治LPS导致的兔急性肺损伤，这种保护作用可能与其抑制肺组织中炎症介质的作用有关。Objective To observe the role of insulin in the prevention and treatment of LPS - induced acute lung injury （ALI ） of rabbit, and further explore the underlying mechanism by which insulin exert protective effects on LPS - induced ALI. Methods New Zealand white rabbit 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^-1· kg^-1 ） . Use microinjection pump to inject solution through ear - edge vein. NS group and LPS group were injected normal saline, and keep on four hours. Insulin ＋ LPS group was injected insulin mixed liquor, and then was instilled LPS intratracheally after 0. 5 h. LPS ＋ insulin group was instilled LPS intratraeheally, and then was injected insulin mixed liquor after 0. 5 h. The insulin mixed liquor continued for four hours. After four and a half hours, the histological changes of lungs were observed, and the left lung wet - to - dry （ W/D ） weight ratios and the protein content in BALF were evaluated. Meanwhile, TNF - α, IL - 6, LDH and MPO in lung homogenate were measured. Results 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, the protein content in BALF, the content of TNF - α IL - 6, LDH and MPO were highly increased in LPS group （ P 〈 0.05 ） , Insulin treatment and prevention could inhibit all these increased parameters （ P 〈 0. 05 ）. Conclusion Insulin could play an important role in prevention and treatment of rabbit ALI induced by LPS, and the mechanism of protection was correlated with inhibition of mediators of inflammation.

关 键 词：急性肺损伤 脂多糖 胰岛素 肿瘤坏死因子-α 白细胞介素-6 乳酸脱氢酶 髓过氧化物酶 

分 类 号：R458.5[医药卫生—治疗学]