氨甲环酸抑制线粒体 DAMPs 的释放，并减轻鼠烧伤模型中的肺部炎症。
Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model.
机构信息
From the Maine Medical Center Research Institute (I.P., D.K., T.S., C.K., K.P.), Scarborough, Maine, and Department of Surgery, Acute Care Surgery Division, Maine Medical Center (M.P., R.K., J.R.), Tufts University School of Medicine, Portland, Maine.
出版信息
J Trauma Acute Care Surg. 2019 Apr;86(4):617-624. doi: 10.1097/TA.0000000000002177.
BACKGROUND
Severe burn injuries are known to initiate a profound systemic inflammatory response (SIRS) that may lead to burn shock and other SIRS-related complications. Damage-associated molecular patterns (DAMPs) are important early signaling molecules that initiate SIRS after burn injury. Previous work in a rodent model has shown that application of a topical immune modulator (p38MAPK inhibitor) applied directly to the burn wound decreases cytokine expression, reduces pulmonary inflammation and edema. Our group has demonstrated that tranexamic acid (TXA)-in addition to its use as an antifibrinolytic-has cell protective in vitro effects. We hypothesized that administration of TXA after burn injury would attenuate DAMP release and reduce lung inflammation.
METHODS
C57/BL6 male mice underwent a 40% Total Body Surface Area (TBSA) scald burn. Sham animals underwent the same procedure in room temperature water. One treatment group received the topical application of p38MAPK inhibitor after burn injury. The other treatment group received an intraperitoneal administration of TXA after burn injury. Animals were sacrificed at 5 hours. Plasma was collected by cardiac puncture. MtDNA levels in plasma were determined by quantitative Polymerase Chain Reaction (qPCR). Syndecan-1 levels in plasma were measured by ELISA. Lungs were harvested, fixed, and paraffin-embedded. Sections of lungs were stained for antigen to detect macrophages.
RESULTS
Topical p38MAPK inhibitor and TXA significantly attenuated mtDNA release. Both TXA and the topical p38MAPK inhibitor reduced lung inflammation as represented by decreased macrophage infiltration. Syndecan-1 levels showed no difference between burn and treatment groups.
CONCLUSION
Both p38 MAPK inhibitor and TXA demonstrated the ability to attenuate burn-induced DAMP release and lung inflammation. Beyond its role as an antifibrinolytic, TXA may have significant anti-inflammatory effects pertinent to burn resuscitation. Further study is required; however, TXA may be a useful adjunct in burn resuscitation.
背景
严重烧伤会引发全身性炎症反应综合征（SIRS），进而导致烧伤休克和其他 SIRS 相关并发症。损伤相关分子模式（DAMPs）是启动烧伤后 SIRS 的重要早期信号分子。之前在啮齿动物模型中的研究表明，直接应用于烧伤创面的局部免疫调节剂（p38MAPK 抑制剂）可降低细胞因子表达，减轻肺部炎症和水肿。我们的研究小组已经证明，氨甲环酸（TXA）——除了作为抗纤维蛋白溶解剂的作用外——在体外具有细胞保护作用。我们假设在烧伤后给予 TXA 可减轻 DAMPs 的释放并减轻肺部炎症。
方法
C57/BL6 雄性小鼠接受 40%总体表面积（TBSA）的烫伤烧伤。假手术组动物在室温水中接受相同的操作。一组治疗组在烧伤后给予 p38MAPK 抑制剂的局部应用。另一组治疗组在烧伤后给予 TXA 的腹腔内给药。动物在 5 小时时处死。通过心脏穿刺收集血浆。通过定量聚合酶链反应（qPCR）测定血浆中的线粒体 DNA（mtDNA）水平。通过 ELISA 测量血浆中 syndecan-1 的水平。收获、固定和石蜡包埋肺。对肺组织切片进行抗原染色以检测巨噬细胞。
结果
局部 p38MAPK 抑制剂和 TXA 显著减轻了 mtDNA 的释放。TXA 和局部 p38MAPK 抑制剂均减少了巨噬细胞浸润，从而减轻了肺部炎症。烧伤和治疗组之间的 syndecan-1 水平没有差异。
结论
p38MAPK 抑制剂和 TXA 均表现出减轻烧伤诱导的 DAMPs 释放和肺部炎症的能力。除了作为抗纤维蛋白溶解剂的作用外，TXA 可能具有与烧伤复苏相关的重要抗炎作用。需要进一步研究，但是，TXA 可能是烧伤复苏的有用辅助手段。
Zotero 插件