[粒细胞-巨噬细胞集落刺激因子对出血性急性肺损伤小鼠多器官中核因子-κB激活的影响]

[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

作者信息

Wang Qian, Song Yong, Shi Yi

机构信息

Department of Respiratory Diseases, Clinical School of First Military Medical University (Guangzhou South Medical University), Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, Jiangsu, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 May;19(5):295-8.

PMID:17490571

Abstract

OBJECTIVE

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice.

METHODS

Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS

22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05).

CONCLUSION

22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

摘要

目的

通过特异性粒细胞-巨噬细胞集落刺激因子（GM-CSF）中和抗体（22E9）和地塞米松（DEX）研究核因子-κB（NF-κB）激活在出血诱导的急性肺损伤（ALI）小鼠多器官中的作用。

方法

选用20只雄性C57BL/6小鼠，通过心脏穿刺建立失血性休克模型。在心脏穿刺前，不同组小鼠分别经鼻给予磷酸盐缓冲溶液（PBS，PCG组）、PBS加1μg 22E9（HS1组）、PBS加10μg 22E9（HS10组）和PBS加20μg DEX（DEX组）。阴性对照组（NCG组）进行心脏穿刺但不造成休克，随后经鼻给予无休克的PBS。失血性休克后4小时采集小鼠的肺、心、肝和肾组织。采用电泳迁移率变动分析（EMSA）测定不同器官中NF-κB的活性。采用酶联免疫吸附测定（ELISA）测定肺和心中的肿瘤坏死因子-α（TNF-α）。

结果

与PCG组相比，低剂量或高剂量的22E9均可显著抑制肺、心和肝中NF-κB的活性，并使肾中NF-κB活性升高（均P<0.05）。HS1组中22E9的作用比HS10组更好（均P<0.05）。与PCG组相比，DEX显著增强了肾中NF-κB的活性（P<0.05），但未显著抑制心和肝中NF-κB的活性。22E9显著抑制肺和心中的TNF-α，而DEX显著抑制心中的TNF-α（均P<0.05）。