Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.
Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.
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DOI：
10.1097/shk.0000000000000319
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Alam HB
中科院分区：
文献类型：
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作者：
Halaweish I;Nikolian V;Georgoff P;Li Y;Alam HB
创伤性损伤及其后遗症是美国和全球死亡率的主要来源。休克、创伤性脑损伤和多发性创伤的初始治疗仅限于复苏液体以补充损失的体积。迄今为止，还没有具有固有促生存特性的治疗方法。我们的实验室已经研究了使用组蛋白去乙酰化酶抑制剂（HDACIs）作为药理学试剂来提高生存率。这类药物通过翻译后蛋白质修饰起作用，是染色质结构和功能以及许多细胞质蛋白质功能的直接调节剂。在失血性休克和多发性创伤模型中，即使在没有液体复苏的情况下，HDACI的给药也提供了显著的生存优势。在出血和脓毒症的两次打击模型以及出血性休克合并创伤性脑损伤中也显示出积极的结果。我们小组和其他人产生的累积数据继续支持使用HDACI来创建促存活表型。随着进一步的研究和临床试验，HDACI有可能成为创伤治疗的一个不可或缺的工具，特别是在院前阶段。
Traumatic injuries and their sequela represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date, there are no treatments with inherent pro-survival properties. Our lab has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for creation of a pro-survival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in treatment of trauma, especially in the pre-hospital phase.