羟乙基淀粉130/0.4对大鼠内毒素性急性肺损伤ICAM-1表达的影响及MAPK信号通路在其中的作用

Effect of hydroxyethyl starch 130/0.4 on ICAM-1 expression in endotoxin-induced acute lung injury in rats and role of MAPK signal pathway in its expression

目的探讨不同剂量羟乙基淀粉溶液(hydroxyethylstarch,HES)130.04对大鼠内毒素性急性肺损伤(acute lunginjury,ALI)肺组织细胞间粘附分子1(intercellular adhesionmolecule1,ICAM-1)表达的影响及丝裂原活化蛋白激酶(mi-togen activated protein kinase,MAPK)通路在其中的作用。方法36只♂SD大鼠,随机分为6组,每组6只,N组(对照组)不给予脂多糖(lipopolysaccharide,LPS),H1、H2、H3、H4组给予LPS后分别按照3.75,7.5,15,30ml.kg-1的剂量持续输入HES130/0.4,L组给予LPS后持续输入生理盐水。于LPS注射4h后处死大鼠,测定肺组织中性粒细胞髓过氧化物酶(MPO)活性、肺湿干重比(W/D)、ICAM-1蛋白和mRNA表达、MAPK激酶活性以及支气管肺泡灌洗液(BALF)中总蛋白和白细胞数。结果与N组比较,L组肺组织MPO活性、W/D比、ICAM-1蛋白和mRNA、p-ERK、p-p38、p-JNK表达以及BALF中总蛋白和白细胞数升高;与L组比较,H1和H2组肺组织和BALF中上述指标降低,其中以7.5ml.kg-1剂量最为明显。结论中小剂量使用HES130/0.4可改善内毒素性急性肺损伤炎症反应,这种作用可能与通过MAPK通路抑制ICAM-1蛋白和mRNA的表达有关。

Aim To examine the effect of different dosages hydroxyethyl starch （HES） 130/0.4 on intercellular adhesion molecule 1 （ICAM-1） expression in lung tissue of acute lung injury in endotoxemic rats and explore the role of MAPKs pathway in its expression. Methods Thirty six healthy Sprague Dawley （SD） rats weighing 270 - 320 g were randomly divided into 6 groups with 6 animals in each group. In group H1-H4, 1 min after lipopolysaccharide （LPS） 5 mg·kg^-1 intravenously administration, HES 130/0. 4 with 3.75, 7, 5,15,30 mg·kg^-1 were infused intravenously respectively at a rate of 0.2 ml · min^-1. In group L, saline instead of HES 130/0. 4 was administered. Group N served as control by giving the same volume of saline. The animals were anesthetized with pentobarbital. Right external jugular vein was injected with LPS. The animals were killed 4 hours after LPS injection for determination of total protein, WBC, MPO, W/D, ICAM-1 protein and mRNA and MAPKs activity. Results Compared with control group, total protein, WBC, MPO, W/D, expression of ICAM-1 protein and mRNA and MAPKs activity were increased significantly in group L. Compared with group L, total protein, WBC, MPO,W/D, expression of ICAM-1 protein and mRNA and MAPKs activity were decreased significantly in group H1 and H2, especially at the dosage of 7.5 ml·kg^-1. Conclusion HES 130/0.4 （7.5 ml·kg^-1） can attenuate inflammatory response of acute lung injury induced by LPS, which may be related with inhibiting the expression of ICAM-1 protein and mRNA through MAPKs signal pathway.