首页|期刊导航|中华医学杂志（英文版）|Antithrombin-Ⅲ without concomitant heparin improves endotoxin-induced acute lung injury rats by inhibiting the activation of mitogen-activated protein kinase
中华医学杂志（英文版）2009，Vol.122Issue(20)：2466-2471,6.DOI:10.3760/cma.j.issn.0366-6999.2009.20.013
Antithrombin-Ⅲ without concomitant heparin improves endotoxin-induced acute lung injury rats by inhibiting the activation of mitogen-activated protein kinase
Antithrombin-Ⅲ without concomitant heparin improves endotoxin-induced acute lung injury rats by inhibiting the activation of mitogen-activated protein kinase
摘要
Abstract
Background Antithrombin-Ⅲ (AT-Ⅲ), the major inhibitor of thrombin in plasma, also has anti-inflammation property and might have positive effect on sepsis. The present study aimed to investigate the effects of AT-Ⅲ on inflammatory reaction and pulmonary protection in endotoxin-induced acute lung injury (ALI) rat.Methods Sixty male Sprague-Dawley rats were randomly assigned equally to normal control group, ALl group, AT-Ⅲ treatment group, AT-Ⅲ+heparin treatment group, and heparin treatment group. The pulmonary vascular permeability index (PVPI) was measured by single nuclide tracer technique. The activity of AT-Ⅲ in plasma was determined by the method of synthetic chromogenic substrata. Tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels in serum were determined by enzyme-linked immunosorbent assay. The expressions of lung tissue mitogen-activated protein kinases (ERK1/2, P38 and JNK MAPK) were determined by Western blotting.Results Rats had significantly improved lung histopathology in the AT-Ⅲ treatment group and heparin treatment group compared with the ALI group. The PVPI of the ALI group was 0.38±0.04, significantly higher than that of the normal control group (0.20±0.02, P <0.01), AT-Ⅲ treatment group (0.30±0.04, P <0.01) and heparin treatment group (0.28±0.04,P <0.01) respectively. There were no significant differences of PVPI in the ALl group and AT-Ⅲ+heparin treatment group.The activity of AT-Ⅲ in plasma in the ALl group was (76±8)%, significantly lower than that of the normal control group ((96±11)%, P <0.05) and AT-Ill treatment group ((105±17)%, P <0.05) respectively. The serum levels of TNF-α and IL-6 of the ALI group were (2.770±0.373) pg/L and (1.615±0.128) ng/ml respectively, significantly higher than those of the normal control group ((0.506±0.093) pg/L and (0.233±0.047) ng/ml respectively, all P <0.01), AT-Ⅲ treatment group ((1.774±0.218) μg/L and (1.140±0145) ng/ml respectively, all P <0.01) and heparin treatment group ((1.924i±0.349) μg/L and (1.223±0.127) ng/ml respectively, all P <0.01). The lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions were markedly higher in the ALI group than in the normal control group, AT-Ⅲ treatment group and heparin treatment group respectively.Conclusions AT-Ⅲ without concomitant heparin inhibited the activation of ERK1/2 and P38 MAPK, down-regulated the levels of downstream cytokines TNF-α and IL-6, relieved endothelial permeability, and improved the ALl in endotoxin-induced rats. It might be helpful to administrate AT-Ⅲ alone, not with concomitant heparin, to those patients with ALI and sepsis.关键词
antithrombin-Ⅲ/ heparin/ mitogen-activated protein kinase/ endotoxin/ acute lung injuryKey words
antithrombin-Ⅲ/ heparin/ mitogen-activated protein kinase/ endotoxin/ acute lung injury分类
医药卫生引用本文复制引用
SUN Hui-ming,HONG Ling-zhi,SHEN Xiao-kun,LIN Xin-qing,SONG Yong,SHI Yi..Antithrombin-Ⅲ without concomitant heparin improves endotoxin-induced acute lung injury rats by inhibiting the activation of mitogen-activated protein kinase[J].中华医学杂志（英文版）,2009,122(20):2466-2471,6.基金项目
This work was supported by a grant from Great Topic Foundation of Jiangsu Province, China (No. 2005A6). （No. 2005A6）
