Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice.
Relative Tissue Factor Deficiency Attenuates Ventilator-Induced Coagulopathy but Does Not Protect against Ventilator-Induced Lung Injury in Mice.
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DOI：
10.1155/2012/130410
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发表时间：
2012
影响因子：
1.7
通讯作者：
Schultz MJ
中科院分区：
文献类型：
--
作者：
Wolthuis EK;Vlaar AP;Choi G;Roelofs JJ;Levi M;Juffermans NP;Schultz MJ
预防组织因子（TF-）介导的全身性凝血病可改善脓毒症模型的结局。预防TF介导的肺凝血病可减轻呼吸机诱导的肺损伤（VILI）。我们研究了相对TF缺乏对VILI小鼠模型肺凝血功能障碍和炎症的影响。 对杂合TF敲除（TF+/-）小鼠及其野生型（TF+/+）同窝小鼠进行镇静（对照）或镇静、气管切开并以低潮气量或高潮气量机械通气5小时。 机械通气导致肺凝血障碍和炎症，潮气量较高的机械通气后损伤更大。与TF+/+小鼠相比，TF+/−小鼠在两个通气组中均表现出显著较低的肺凝血酶-抗凝血酶复合物水平。然而，TF+/−和TF+/+小鼠之间的肺湿干比、BALF总蛋白水平、中性粒细胞内流和肺组织病理学评分无差异。值得注意的是，与TF+/+小鼠相比，TF+/−小鼠的肺细胞因子水平显著更高。TF的相对缺乏没有改变细胞因子的全身水平。TF缺乏与肺凝血功能下降相关，与通气策略无关。然而，相对TF缺乏并不能减少VILI，实际上会导致更高的肺炎症介质水平。
Preventing tissue-factor-(TF-) mediated systemic coagulopathy improves outcome in models of sepsis. Preventing TF-mediated pulmonary coagulopathy could attenuate ventilator-induced lung injury (VILI). We investigated the effect of relative TF deficiency on pulmonary coagulopathy and inflammation in a murine model of VILI. Heterozygous TF knockout (TF+/−) mice and their wild-type (TF+/+) littermates were sedated (controls) or sedated, tracheotomized, and mechanically ventilated with either low or high tidal volumes for 5 hours. Mechanical ventilation resulted in pulmonary coagulopathy and inflammation, with more injury after mechanical ventilation with higher tidal volumes. Compared with TF+/+ mice, TF+/− mice demonstrated significantly lower pulmonary thrombin-antithrombin complex levels in both ventilation groups. There were, however, no differences in lung wet-to-dry ratio, BALF total protein levels, neutrophil influx, and lung histopathology scores between TF+/− and TF+/+ mice. Notably, pulmonary levels of cytokines were significantly higher in TF+/− as compared to TF+/+ mice. Systemic levels of cytokines were not altered by the relative absence of TF. TF deficiency is associated with decreased pulmonary coagulation independent of the ventilation strategy. However, relative TF deficiency does not reduce VILI and actually results in higher pulmonary levels of inflammatory mediators.