P-Selectin Is Critical for De Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma
P-Selectin Is Critical for De Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma
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DOI：
10.1097/ta.0000000000002166
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Brown, Ian E.
中科院分区：
文献类型：
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作者：
Schutzman, Linda M.;Rigor, Robert R.;Brown, Ian E.
背景肺动脉血管系统内的血栓栓塞事件是严重钝性胸部创伤的棘手并发症。这些事件的潜在机制目前仍存在疑问，因为在这种特定的创伤人群中，肺血栓栓塞事件往往被诊断得更快、更频繁，并且没有相关的全身血栓形成。本研究通过使用体内阻断抗体研究P-选择素在血栓形成中的作用。我们假设P-选择素在钝性胸部创伤后新发肺动脉血栓形成中起关键作用。方法采用小鼠胸部侧面钝性创伤失重模型。实验组中的野生型小鼠在创伤前给予针对P-选择素的阻断抗体。所有小鼠在24小时处以安乐死，以用苏木精-伊红染色或免疫荧光染色评估纤维蛋白和P-选择素。结果：与未受伤的假手术小鼠相比，未接受P-选择素抗体的损伤小鼠显示出在政变和对冲组织中纤维蛋白积累的四倍至五倍的稳健增加（每μ m动脉壁的荧光）。相比之下，用P-选择素阻断抗体预处理的小鼠在钝性胸部创伤后肺两侧的纤维蛋白积累没有显著增加。在接受P-选择素阻断抗体的假手术对照组和接受同种型对照抗体的假手术对照组之间没有发现平均纤维蛋白沉积的差异。结论钝性胸部创伤后肺动脉管腔表面P-选择素表达增加。此外，体内P-选择素阻断可防止钝性胸部创伤后肺动脉纤维蛋白积聚，证实P-选择素是创伤性损伤后新生肺动脉血栓形成所必需的。
BACKGROUND Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.