RECOMBINANT HUMAN SOLUBLE TUMOR NECROSIS FACTOR-ALPHA RECEPTOR FUSION PROTEIN PARTLY ATTENUATES VENTILATOR-INDUCED LUNG INJURY
RECOMBINANT HUMAN SOLUBLE TUMOR NECROSIS FACTOR-ALPHA RECEPTOR FUSION PROTEIN PARTLY ATTENUATES VENTILATOR-INDUCED LUNG INJURY
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DOI：
10.1097/shk.0b013e31817d42dd
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发表时间：
2009-03-01
期刊：
影响因子：
3.1
通讯作者：
Schultz, Marcus J.
中科院分区：
文献类型：
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作者：
Wolthuis, Esther K.;Vlaar, Alexander P. J.;Schultz, Marcus J.
呼吸机诱导的肺损伤至少部分由TNF-α介导。我们确定了重组人可溶性TNF受体融合蛋白（依那西普）对机械通气（MV）诱导的小鼠呼吸机诱导的肺损伤模型的影响。依那西普或安慰剂预处理后，将C57 BI/6小鼠麻醉并随机分配至低潮气量（V-T，类似于7.5 mL/kg）或高V-T（类似于15 mL/kg）MV 5 h。仪器但自主呼吸的小鼠作为对照。终点是肺湿干比、肺组织病理学评分、蛋白水平、支气管肺泡灌洗液（BALF）中中性粒细胞计数和凝血酶-抗凝血酶复合物水平以及肺匀浆中细胞因子水平。半胱天冬酶3阳性细胞的数量被用作细胞凋亡的量度。依那西普治疗减弱MV诱导的变化，特别是在具有高V-T的MV中。与安慰剂相比，依那西普可降低BALF中中性粒细胞数量、BALF中凝血酶-抗凝血酶复合物水平和肺匀浆中细胞因子水平。然而，依那西普治疗对肺湿干比、组织病理学评分和BALF中的局部蛋白水平没有影响。依那西普处理的动物中caspase 3阳性细胞的数量显著更高。依那西普对TNF的抑制部分减弱了MV诱导的变化。
Ventilator-induced lung injury is mediated, at least in part, by TNF-alpha. We determined the effect of a recombinant human soluble TNF receptor fusion protein (etanercept) on mechanical ventilation (MV)-induced changes in a murine ventilator-induced lung injury model. After pretreatment with etanercept or placebo, C57BI/6 mice were anesthetized and randomized to MV with either low tidal volumes (V-T, similar to 7.5 mL/kg) or high V-T (similar to 15 mL/kg) for 5 h. Instrumented but spontaneously breathing mice served as controls. End points were lung wet-to-dry ratios, lung histopathology scores, protein levels, neutrophil cell counts and thrombin-antithrombin complex levels in bronchoalveolar lavage fluid (BALF), and cytokine levels in lung homogenates. The number of caspase 3-positive cells was used as a measure for apoptosis. Etanercept treatment attenuated MV-induced changes, in particular, in MV with high V-T. Compared with placebo, etanercept reduced the number of neutrophils in BALF and thrombin-antithrombin complex levels in BALF and cytokine levels in lung homogenates. Lung wet-to-dry ratios, histopathology scores, and local protein levels in BALF, however, were not influenced by etanercept treatment. The number of caspase 3-positive cells was significantly higher in etanercept-treated animals. Inhibition of TNF by etanercept attenuates, in part, MV-induced changes.