失血性休克肺组织IκB激酶-β表达及山莨菪碱干预研究

Effect of 654-2 on IκB kinase-β expression in lung tissues of rabbits with hemorrhagic shock

目的 探讨IκB激酶 β(IKK β)在失血性休克继发急性肺损伤中的意义及山莨菪碱( 65 4 2 )的干预作用。方法 采用原位杂交、免疫组织化学结合原位定量分析以及酶联免疫吸附试验分别检测模型组、干预组、对照组肺组织IKK β、核因子 (NF) κB表达以及血浆肿瘤坏死因子 α(TNF α)含量 ,并行病理学光镜检查。结果 模型组上述指标依次为 [( 0 .1685± 0 .0 164 )、( 0 .14 69± 0 .0 0 83 )、( 63 6.72± 10 0 .2 3 )ng/L] ,较对照组升高 (P <0 .0 1) ,肺组织有明显炎症改变 ;干预组上述指标依次为 [( 0 .1115± 0 .0 2 87)、( 0 .10 12± 0 .0 0 5 7)、( 3 92 .3 5± 92 .44 )ng/L] ,较模型组降低 (P <0 .0 1) ,肺组织炎症改变减轻。结论 IKK β/NF κB/TNF α效应是失血性休克继发急性肺损伤的重要机制 ;65 4 2可下调IKK β/NF κB通路减轻失血性休克后的急性肺损伤。

Objective To investigate the significance of IKK β in acute lung injury (ALI) following hemorrhagic shock (HS) and the protective effect of Anisodamine (654-2).Methods Twenty-seven rabbits were randomly divided into three groups: HS plus endotoxin group ( n =9),654-2 treatment group ( n =9) and the normal group ( n =9).By using in situ hybridization and immunohitochemistry combined with in situ quantitative analysis,the distribution and relative contents of IKK-β and NF-κB in lung tissues were determined; The concentration of tumor necrosis factor-α (TNF-α) in the plasma was measured by enzyme linked immune adsorbing analysis (ELISA); The pathological changes of lung tissues were examined under a light microscope.Results Compared with the normal group,the expression levels of IKK-β (0.168 5±0.016 4) and NF-κB (0.146 9±0.008 3),the level of TNF-α(636.72±100.23) were obviously increased in HS plus endotoxin group ( P <0.01); 654-2 treatment could inhibit the expression of IKK-β (0.111 5±0.028 7) and NF-κB (0.101 2±0.005 7),significantly decrease the concentration of TNF-α (392.35±92.24),and alleviate the lung injury observed by histological examination.Conclusion IKK-β plays a crucial roles in ALI following HS.654-2 can down-regulate the IKK-β/NF-κB pathway,relieve ALI mediated by TNF-α.