Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion.
Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion.
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DOI：
10.1016/j.resuscitation.2011.07.029
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发表时间：
2012-02
期刊：
影响因子：
6.5
通讯作者：
Alam, Hasan B.
中科院分区：
文献类型：
--
作者：
Kim, Kyuseok;Li, Yongqing;Jin, Guang;Chong, Wei;Liu, Baoling;Lu, Jennifer;Lee, Kyoungbun;deMoya, Marc;Velmahos, George C.;Alam, Hasan B.
急性肺损伤（acute lung injury，ALI）是一种常见的并发症，其发病率和死亡率都很高。丙戊酸（Valproic acid，VPA）是一种抗癫痫药物，在多种缺血/再灌注（ischemia/reperfusion，I/R）模型中具有抗氧化和抗炎作用。本研究旨在探讨丙戊酸钠对大鼠肠I/R急性肺损伤存活和发展的影响。进行了两个实验。实验I：对雄性Sprague-Dawley大鼠（250 - 300 g）进行肠缺血（1小时）和再灌注（3小时）。在缺血后30分钟将其随机分为2组（n = 7/组）：溶媒（Veh）和VPA（300 mg/kg，IV）。本研究的主要终点是缺血开始后4小时内的存活率。实验二：在肠I/R损伤后3小时（1小时缺血+2小时再灌注）检查VPA处理对肺的组织学和生物化学作用（Veh对比VPA，n = 9/组）。采用客观的组织学评分对ALI的程度进行分级。采用酶联免疫吸附试验（ELISA）检测血清细胞因子白细胞介素（IL-6和IL-10）、肺组织中性粒细胞趋化因子（CINC）和髓过氧化物酶（MPO）水平。此外，分析了8-异前列烷的活性，用于肺氧化损伤。在实验I中，VPA给药动物的4小时存活率显著高于Veh动物（71.4% vs. 14.3%，p = 0.006）。在实验II中，ALI在所有Veh组动物中均明显。VPA治疗预防了ALI的发生，组织学评分降低（3.4 ± 0.3 vs. 5.3 ± 0.6，p = 0.025）。此外，与Veh对照组相比，VPA组动物的血清IL-6水平降低（952 ± 213 vs. 7709 ± 1990 pg/ml，p = 0.011）和CINC的肺组织浓度（1188 ± 28对比1298 ± 27，p <0.05）、MPO活性（368 ± 23对比490 ± 29，p <0.05）和8-异前列烷水平（1495 ± 221对比2191 ± 177 pg/ml，p <0.05）。VPA治疗可改善肠I/R损伤大鼠模型的存活率并减轻ALI，至少部分是通过其抗氧化和抗炎作用。
Acute lung injury (ALI) is developed in many clinical situations and associated with significant morbidity and mortality. Valproic acid (VPA), a well-known anti-epileptic drug, has been shown to have anti-oxidant and anti-inflammatory effects in various ischemia/reperfusion (I/R) models. The purpose of this study was to investigate whether VPA could affect survival and development of ALI in a rat model of intestinal I/R. Two experiments were performed. Experiment I: Male Sprague-Dawley rats (250–300 g) were subjected to intestinal ischemia (1 hour) and reperfusion (3 hours). They were randomized into 2 groups (n=7/group) 30 min after ischemia: Vehicle (Veh) and VPA (300 mg/kg, IV). Primary end-point for this study was survival over 4 hours from the start of ischemia. Experiment II: The histological and biochemical effects of VPA treatment on lungs were examined 3 hours (1 hr ischemia + 2 hrs reperfusion) after intestinal I/R injury (Veh vs. VPA, n = 9/group). An objective histological score was used to grade the degree of ALI. Enzyme linked immunosorbent assay (ELISA) was performed to measure serum levels of cytokine interleukins (IL-6 and 10), and lung tissue of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO). In addition, the activity of 8-isoprostane was analyzed for pulmonary oxidative damage. In Experiment I, four-hour survival rate was significantly higher in VPA treated animals compared to Veh animals (71.4% vs. 14.3%, p = 0.006). In Experiment II, ALI was apparent in all of the Veh group animals. Treatment with VPA prevented the development of ALI, with a reduction in the histological score (3.4 ± 0.3 vs. 5.3 ± 0.6, p = 0.025). Moreover, compared to the Veh control group the animals from the VPA group displayed decreased serum levels of IL-6 (952 ± 213 vs. 7709 ± 1990 pg/ml, p = 0.011), and lung tissue concentrations of CINC (1188 ± 28 vs. 1298 ± 27, p < 0.05), MPO activity (368 ± 23 vs. 490 ± 29, p <0.05) and 8-isoprostane levels (1495 ± 221 vs. 2191 ± 177 pg/ml, p < 0.05). VPA treatment improves survival and attenuates ALI in a rat model of intestinal I/R injury, at least in part, through its anti-oxidant and anti-inflammatory effects.
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
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DOI：
10.1124/jpet.107.120188
发表时间：
2007-06-01
影响因子：
3.5
作者：
Kim, Hyeon Ju;Rowe, Michael;Chuang, De-Maw
通讯作者：
Chuang, De-Maw