Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida, USA.
J Neurotrauma. 2021 Mar;38(5):646-654. doi: 10.1089/neu.2020.7257. Epub 2020 Aug 11.
Traumatic brain injury (TBI) patients frequently develop cardiopulmonary system complications such as acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, the mechanism by which TBI causes ALI/ARDS is not fully understood. Here, we used a severe TBI model to examine the effects of a low-molecular-weight heparin, enoxaparin, on inflammasome activation and lung injury damage. We investigated whether enoxaparin inhibits ALI and inflammasome signaling protein expression in the brain and lungs after TBI in mice. C57/BL6 mice were subjected to severe TBI and were treated with vehicle or 1 mg/kg of enoxaparin 30 min after injury. Lung and brain tissue were collected 24 h post-TBI and were analyzed by immunoblotting for expression of the inflammasome proteins, caspase-1 and interleukin (IL)-1β. In addition, lung tissue was collected for histological analysis to determine ALI scoring and neutrophil and macrophage infiltration post-injury. Our data show that severe TBI induces increased expression of inflammasome proteins caspase-1 and IL-1β in the brain and lungs of mice after injury. Treatment with enoxaparin attenuated inflammasome expression in the brain and lungs 24 h after injury. Enoxaparin significantly decreased ALI score as well as neutrophil and macrophage infiltration in lungs at 24 h after injury. This study demonstrates that enoxaparin attenuates ALI and inhibits inflammasome expression in the brain and lungs after TBI. These findings support the hypothesis that inhibition of the neural-respiratory inflammasome axis that is activated after TBI may have therapeutic potential.
创伤性脑损伤 (TBI) 患者常发生心肺系统并发症，如急性肺损伤 (ALI)/急性呼吸窘迫综合征 (ARDS)。然而，TBI 导致 ALI/ARDS 的机制尚未完全阐明。在这里，我们使用严重 TBI 模型来研究低分子量肝素依诺肝素对炎症小体激活和肺损伤的影响。我们研究了依诺肝素是否抑制 TBI 后小鼠脑和肺中的 ALI 和炎症小体信号蛋白表达。C57/BL6 小鼠接受严重 TBI，并在损伤后 30 分钟用载体或 1mg/kg 的依诺肝素处理。TBI 后 24 小时收集肺和脑组织，通过免疫印迹分析炎症小体蛋白、半胱天冬酶-1 和白细胞介素 (IL)-1β 的表达。此外，收集肺组织进行组织学分析，以确定损伤后 ALI 评分以及中性粒细胞和巨噬细胞浸润。我们的数据表明，严重 TBI 诱导损伤后小鼠脑和肺中炎症小体蛋白半胱天冬酶-1 和 IL-1β 的表达增加。依诺肝素治疗可减轻损伤后 24 小时脑和肺中的炎症小体表达。依诺肝素可显著降低损伤后 24 小时的 ALI 评分以及肺中的中性粒细胞和巨噬细胞浸润。本研究表明，依诺肝素可减轻 TBI 后 ALI，并抑制脑和肺中的炎症小体表达。这些发现支持这样一种假设，即抑制 TBI 后激活的神经呼吸炎症小体轴可能具有治疗潜力。
