TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile dysfunction.
TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile dysfunction.
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DOI：
10.1152/ajpheart.01107.2001
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发表时间：
2002-10
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影响因子：
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通讯作者：
James A. Thomas;M. Tsen;D. White;Jureta W. Horton
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作者：
James A. Thomas;M. Tsen;D. White;Jureta W. Horton
大面积烧伤和严重革兰氏阴性脓毒症都与急性心肌收缩功能障碍有关。因为其他人报道烧伤后可能会出现短暂的内毒素血症，我们假设细菌内毒素诱导烧伤后的收缩障碍。我们在两种啮齿动物模型中测试了这一假设。在每个模型中，烧伤后心肌收缩力进行了评估，使用Langendorff制备的离体心脏。在第一个模型中，表达Toll样受体4（TLR 4）（哺乳动物内毒素受体的关键元件）的突变形式或不表达TLR 4的小鼠对烧伤后心肌收缩功能障碍具有抵抗力。在第二个模型中，从烧伤后30分钟或4小时开始，向大鼠输注重组杀菌/通透性增加蛋白（rBPI（21）），一种结合和中和内毒素的蛋白质。rBPI（21）处理动物的心脏完全免受烧伤后收缩损伤。由于烧伤引起的收缩功能障碍可以通过阻断内毒素受体的信号传导或通过中和循环LPS来预防，因此细菌内毒素可能有助于烧伤后心肌收缩力受损。
Both large burns and severe gram-negative sepsis are associated with acute myocardial contractile dysfunction. Because others have reported that burn injury may be followed by transient endotoxemia, we hypothesized that bacterial endotoxin induces contractile impairment after burn trauma. We tested this hypothesis in two rodent models. In each model, postburn myocardial contractility was assessed using Langendorff preparations of excised hearts. In the first model, mice expressing either a mutant form of or no Toll-like receptor 4 (TLR4), a critical element of the mammalian endotoxin receptor, were resistant to postburn myocardial contractile dysfunction. In the second model, starting 30 min or 4 h after burn injury, rats were infused with recombinant bactericidal/permeability-increasing protein (rBPI(21)), a protein that binds and neutralizes endotoxin. Hearts from rBPI(21)-treated animals were completely protected from postburn contractile impairment. Because burn-induced contractile dysfunction can be prevented either by blocking signaling through the endotoxin receptor or by neutralizing circulating LPS, bacterial endotoxin may contribute to impaired myocardial contractility after burn injury.