Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Shock. 2019 Sep;52(3):300-306. doi: 10.1097/SHK.0000000000001308.
Trauma remains a leading cause of morbidity and mortality among all age groups in the United States. Hemorrhagic shock and traumatic brain injury (TBI) are major causes of preventable death in trauma. Initial treatment involves fluid resuscitation to improve the intravascular volume. Although crystalloids may provide volume expansion, they do not have any pro-survival properties. Furthermore, aggressive fluid resuscitation can provoke a severe inflammatory response and worsen clinical outcomes. Due to logistical constraints, however, definitive resuscitation with blood products is often not feasible in the prehospital setting-highlighting the importance of adjunctive therapies. In recent years, histone deacetylase inhibitors (HDACis) have shown promise as pharmacologic agents for use in both trauma and sepsis. In this review, we discuss the role of histone deacetylases (HDACs) and pharmacologic agents that inhibit them (HDACis). We also highlight the therapeutic effects and mechanisms of action of HDACis in hemorrhagic shock, TBI, polytrauma, and sepsis. With further investigation and translation, HDACis have the potential to be a high-impact adjunctive therapy to traditional resuscitation.
在美国，创伤仍然是所有年龄段人群发病率和死亡率的主要原因。失血性休克和创伤性脑损伤（TBI）是创伤中可预防死亡的主要原因。初始治疗包括液体复苏以增加血管内容量。虽然晶体液可能提供容量扩张，但它们没有任何生存益处。此外，积极的液体复苏会引发严重的炎症反应，从而恶化临床结果。然而，由于后勤限制，在院前环境中通常无法进行明确的血液制品复苏——这凸显了辅助治疗的重要性。近年来，组蛋白去乙酰化酶抑制剂（HDACi）作为治疗创伤和脓毒症的药物已显示出良好的应用前景。在这篇综述中，我们讨论了组蛋白去乙酰化酶（HDACs）的作用以及抑制它们的药物（HDACi）。我们还强调了 HDACi 在失血性休克、TBI、多发伤和脓毒症中的治疗效果和作用机制。随着进一步的研究和转化，HDACi 有可能成为传统复苏的一种高影响力的辅助治疗方法。
