摘要
目的探讨特异性抗粒细胞-巨噬细胞集落刺激因子（GM—CSF）的抗体（22E9）和地塞米松（DEX）对失血性休克诱导急性肺损伤（ALI）小鼠肾、肝、心、肺组织核转录因子-κB（NF-κB）活化的影响，为失血性休克继发的多器官损伤防治提供理论依据。方法C57BL／6雄性小鼠20只，用心脏穿刺致失血性休克诱导ALI小鼠模型。制模前经鼻分别滴入磷酸盐缓冲液（PBS，PCG组）、PBS＋1μg 22E9（HS1组）、PBS＋10pg22E9（HS10组）、PBS＋20μgDEX（DEX组）进行干预，阴性空白对照组（NCG组）经鼻滴入PBS后仅予心脏穿刺。休克4h时采用凝胶电泳迁移率改变分析法（EMSA）检测肺、心、肝、肾组织NF—κB活性；用酶联免疫吸附法（ELISA）检测肺、心组织肿瘤坏死因子-α（TNF—α）含量。结果与PCG组比较，高、低剂量22E9均可显著抑制肝、心、肺组织NF—κB活性，且低剂量的抑制效果比高剂量明显，同时可增加肾组织NF—κB活性（P均〈0．05）。DEX可增强肾、肝组织NF—κB活性（P均〈0．05），但与PCG组比较，DEX对肾、肝、肺组织NF—κB活性未见明显的抑制作用。22E9干预可显著抑制心、肺组织TNF—α含量的升高，DEX仅能有效抑制心组织TNF—α含量（P均〈0．05）。结论22E9能显著抑制失血性休克诱导ALI小鼠多器官组织NF-κB的活化及炎症反应，减少失血性休克引起的多器官损伤；DEX的抑制作用不显著。
Objective To investigate the effects of nuclear factor - κB （NF - κB） 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 1μg 22E9 （HS1 group）, PBS plus 10 μg 22E9 （HS10 group） and PBS plus 20 μg 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 - κB in different organs was determined by electrophoretic mobility shift assay （EMSA）. The tumor necrosis factor - α （TNF - α） in lung and heart were determined by enzyme - linked immunosorbent assay （ELISA）. Results 22E9 in both low or high doses could significantly inhibit NF - κB activities in lung, heart and liver, and elevated NF -κB 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 - κB activity in kidney （P（0.05） and didn＇t significantly inhibit NF - κB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF - α in lung and heart, while DEX significantly inhibited TNF-α in heart （all P〈0.05）. Conclusion 22E9 can inhibit the NF - κB activation and inflammatory reaction in multiple organs after hemorrhage -induced ALI and reduce injury in multiple organs, while DEX has no significant effect.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第5期295-298,I0001,共5页
Chinese Critical Care Medicine
基金
江苏省自然科学基金资助项目（BK2004096）
