Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock
Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock
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DOI：
10.1097/ta.0000000000001763
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Alam, Hasan B.
中科院分区：
文献类型：
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作者：
Georgoff, Patrick E.;Nikolian, Vahagn C.;Alam, Hasan B.
背景：丙戊酸（VPA）是一种组蛋白脱乙酰酶抑制剂，可改善大型动物创伤模型的结果。然而，其保护作用机制尚不完全清楚。我们试图描述创伤性损伤后 VPA 治疗引起的基因变化。 方法：六头雌性约克夏猪遭受创伤性脑损伤（控制性皮质冲击）、多发伤（肝和脾撕裂、肋骨骨折、直肌挤压）和失血性休克（HS，总血容量的 40%）。 HS 2 小时后，动物随机接受生理盐水 (NS) 或 NS + 150 mg/kg 静脉注射 VPA 复苏（n = 3/队列，总共 18 个样本）。在三个不同的时间点收集血样以分离外周血单核细胞：基线、受伤后 6 小时以及受伤后第一天。从外周血单核细胞中提取 RNA 并进行测序。差异表达分析（错误发现率 < 0.001 且 p 值
BACKGROUND: Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma. However, its protective mechanism of action is not completely understood. We sought to characterize the genetic changes induced by VPA treatment following traumatic injuries.METHODS: Six female Yorkshire swine were subjected to traumatic brain injury (controlled cortical impact), polytrauma (liver and splenic laceration, rib fracture, rectus crush), and hemorrhagic shock (HS, 40% total blood volume). Following 2 hours of HS, animals were randomized to resuscitation with normal saline (NS) or NS + 150 mg/kg of intravenous VPA (n = 3/cohort, 18 samples total). Blood samples were collected for isolation of peripheral blood mononuclear cells at three distinct time points: baseline, 6 hours following injuries, and on postinjury day 1. RNA was extracted from peripheral blood mononuclear cells and sequenced. Differential expression analysis (false discovery rate < 0.001 and p value