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目的探讨失血性休克合并内毒素血症诱发急性肺损伤(ALI)兔肺 cAMP 反应元件结合蛋白(cREB)表达和活性的变化。方法采用家兔失血性休克合并内毒素血症诱发肺损伤模型,36只家兔随机分为:造模后2h 组,造模后12h 组和对照组。分析动脉血氧分压(PaO_2)、肺湿重/干重(W/D)和肺组织病理学改变,用酶联免疫吸附法(ELISA)检测肺组织匀浆肿瘤坏死因子(TNF)-α含量,Western 印迹检测肺组织 CREB 蛋白的表达,凝胶电泳迁移率(EMSA)法检测 CREB/DNA 结合活性。结果病理学显示造模后12h 组肺泡结构破坏,肺泡壁和肺间质内有大量中性粒细胞浸润和较多红细胞渗出,造模后2h 组病变轻微。造模后12h 组 PaO_2显著低于对照组(55.0±11.0mm Hgvs 92.9±14.6 mm Hg;P<0.01),W/D 高于对照组(5.5±1.1 vs 3.5±0.8;P<0.01),而造模后2h组与对照组比较变化不明显;造模后12h 组肺组织匀浆中 TNF-α含量显著高于对照组(491.6±59.2pg/ml vs 159.3±44.9pg/ml;P<0.01),而造模后2h 组与对照组比较变化不明显。造模后2h 组和12h 组肺组织 CREB 蛋白的表达量均显著高于对照组(0.874±0.182,0.775±0.258 vs 0.483±0.199;P<0.01),造模后2h 组和12h 组 CREB/DNA 结合活性也显著高于对照组(355±79,330±108 vs 185±68;P<0.01)。结论失血性休克合并内毒素血症促进了肺组织 CREB 的表达和活化,CREB 可能通过促进炎症因子的表达而参与了急性肺损伤的炎症反应过程。
Objective To investigate the expression of cREB and the activity of cREB in acute lung injury (ALI) induced by hemorrhagic shock combined with endotoxemia. Methods Rabbit hemorrhagic shock with endotoxemia induced lung injury model, 36 rabbits were randomly divided into: 2h after modeling, 12h after modeling and control group. PaO2, W / D and histopathological changes of lung tissue were analyzed. Tumor necrosis factor (TNF) -alpha was detected by enzyme-linked immunosorbent assay (ELISA) The expression of CREB protein in lung tissue was detected by Western blot. The CREB / DNA binding activity was detected by electrophoretic mobility shift assay (EMSA). Results The pathology showed that the alveolar structure was destroyed 12h after model establishment. There were a large number of neutrophil infiltration and more erythrocyte exudation in the alveolar wall and interstitium, and the lesion was slight at 2h after modeling. The PaO_2 of 12h after modeling was significantly lower than that of the control group (55.0 ± 11.0mm Hg vs 92.9 ± 14.6 mm Hg; P <0.01), and W / D was higher than that of the control group (5.5 ± 1.1 vs 3.5 ± 0.8; P <0.01) The level of TNF-αin lung homogenate 12h after modeling was significantly higher than that in control group (491.6 ± 59.2pg / ml vs 159.3 ± 44.9pg / ml; P <0.01 ), While the 2h group after modeling did not change significantly compared with the control group. The expression of CREB protein in lung tissue of 2h and 12h after model making were significantly higher than that of control group (0.874 ± 0.182, 0.775 ± 0.258 vs 0.483 ± 0.199; P <0.01) The binding activity was also significantly higher than that of the control group (355 ± 79,330 ± 108 vs 185 ± 68; P <0.01). Conclusions Hemorrhagic shock combined with endotoxemia promotes the expression and activation of CREB in lung tissue. CREB may be involved in the inflammatory reaction of acute lung injury by promoting the expression of inflammatory cytokines.