Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.
Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.
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DOI：
10.1016/j.jss.2021.04.014
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Alam HB
中科院分区：
文献类型：
--
作者：
Biesterveld BE;Siddiqui AZ;O'Connell RL;Remmer H;Williams AM;Shamshad A;Smith WM;Kemp MT;Wakam GK;Alam HB
创伤是年轻人死亡的主要原因。这些患者肾损伤的发生率很高，这单独增加了死亡的风险。由于丙戊酸（VPA）治疗已被证明可以提高致死性创伤动物模型的存活率，我们假设它也可以减轻急性肾损伤的程度。我们分析了来自两个独立实验的数据，在这些实验中，猪受到致命的侮辱。模型1：出血（50%血容量出血，72小时损伤控制复苏）。模型2：多发伤（外伤性脑损伤，40%血容量出血，股骨骨折，直肌挤压，V级肝裂伤）。两个模型均在1小时休克期后用生理盐水(NS) +/ - VPA 150 mg/kg进行复苏（n=5-6/组）。在Liasys 330化学分析仪上用比色法分析血清肌酐（Cr）。对尸检时采集的肾组织进行蛋白质组学分析。VPA治疗显著提高了两种模型的生存率（p<0.05）。（模型1:80% vs 20%；模型2:83% vs 17%）。模型1（单独出血）：出血后8小时，NS对照动物的Cr从基线1.2上升到3.0 (p<0.0001)，而VPA治疗动物的Cr仅上升到2.1 （p=0.004）。模型2（多发伤）：损伤后4小时，NS对照动物的Cr水平从基线1.3 mg/dL上升到2.5 mg/dL (p = 0.01)，而VPA处理动物的Cr水平仅上升到1.8 mg/dL （p = 0.02）。肾脏组织的蛋白质组学分析发现，VPA治疗对代谢途径的影响最大。单剂量VPA （150 mg/kg）对猪多伤和失血性休克模型的急性肾损伤有显著的保护作用。
Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. We analyzed data from two separate experiments where swine were subjected to lethal insults. Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-hour damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/− VPA 150 mg/kg after a 1-hour shock phase in both models (n=5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. VPA treatment significantly (p<0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (p<0.0001) 8 hours after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (p=0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (p = 0.01) in NS control animals 4 hours after injury but rose to only 1.8 in VPA treated animals (p = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.
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影响因子：
2.9
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.2
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