Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model.
Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model.
复制标题
丙戊酸可预防缺血再灌注损伤模型中的肾功能障碍和炎症。
DOI：
10.1155/2016/5985903
复制
发表时间：
2016
影响因子：
--
通讯作者：
Noronha IL
中科院分区：
文献类型：
--
作者：
Costalonga EC;Silva FM;Noronha IL
缺血再灌注损伤(IRI)是急性肾损伤(AKI)的主要致病因素。目前，还没有有效的治疗方法来预防AKI。本研究的目的是分析具有抗炎作用的组蛋白去乙酰酶抑制剂丙戊酸(VPA)是否能预防肾脏IRI。雄性Wistar大鼠分为3组：假手术组、缺血再灌注45 组和丙戊酸+丙戊酸联合用药组，缺血前2天给予丙戊酸300 mg/kg，每日2次。IRI后48小时处死动物。VPA可减轻缺血后肾功能障碍，表现为IRI+VPA组BUN(mg/dL)、血肌酐(mg/dL)和FENA(%)的下降(分别为39±11、0.5±0.05和0.5±0.06，P<0.05)。与缺血再灌注组比较，P<；0.001。此外，与缺血再灌注组相比，缺血再灌注+丙戊酸组的急性肾小管坏死分级和凋亡细胞数显著降低(p<；0.001)。此外，VPA治疗减少了炎性细胞的浸润和促炎细胞因子的表达。这些数据表明，VPA可预防与肾IRI相关的肾功能障碍和炎症。
Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). At present, there are no effective therapies to prevent AKI. The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI. Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI. Animals were euthanized at 48 hours after IRI. VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group (39 ± 11, 0.5 ± 0.05, and 0.5 ± 0.06, resp.) compared with the IRI group (145 ± 35, 2.7 ± 0.05, and 4.9 ± 1, resp.; p < 0.001). Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group (p < 0.001). Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines. These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI.