Zheng Qiang, Liu Wei, Liu Zhenning, Zhao Hongyu, Han Xinfei, Zhao Min
Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
J Surg Res. 2014 Nov;192(1):163-9. doi: 10.1016/j.jss.2014.05.030. Epub 2014 May 20.
Valproic acid (VPA), a histone deacetylase inhibitor, has extensive activities against inflammation, oxidation, and malignancy. This study was designed to investigate the protective effect of VPA on the systemic inflammatory response and renal injury in septic mice.
The septic model of mice was established using a cecal ligation-puncture technique. A single dose of VPA (300 mg/kg) was administered at 30 min postoperatively.
We found that VPA reduced the tubular swelling and lowered the serum levels of blood urea nitrogen, creatinine, and C-reactive protein. After treatment with VPA, the renal level of malondialdehyde and the activity of myeloperoxidase decreased markedly; the activity of superoxide dismutase and the glutathione content increased accordingly; and the serum levels of tumor necrosis factor α, interleukin 1β, and interleukin 6 decreased markedly. Furthermore, VPA suppressed the renal expression of cyclooxygenase 2 and inducible nitric oxide synthase and repressed the release of prostaglandin E2 and nitric oxide.
Our results demonstrate that VPA reduces the inflammatory response in a septic model and protects mice from renal injury, showing substantial potential in the treatment of sepsis.
丙戊酸（VPA）是一种组蛋白去乙酰化酶抑制剂，具有广泛的抗炎、抗氧化和抗肿瘤活性。本研究旨在探讨VPA对脓毒症小鼠全身炎症反应和肾损伤的保护作用。
采用盲肠结扎穿刺技术建立小鼠脓毒症模型。术后30分钟给予单次剂量的VPA（300mg/kg）。
我们发现VPA减轻了肾小管肿胀，降低了血清尿素氮、肌酐和C反应蛋白水平。VPA治疗后，肾组织丙二醛水平和髓过氧化物酶活性明显降低；超氧化物歧化酶活性和谷胱甘肽含量相应增加；血清肿瘤坏死因子α、白细胞介素1β和白细胞介素6水平明显降低。此外，VPA抑制了肾组织中环氧化酶2和诱导型一氧化氮合酶的表达，并抑制了前列腺素E2和一氧化氮的释放。
我们的结果表明，VPA可减轻脓毒症模型中的炎症反应，保护小鼠免受肾损伤，在脓毒症治疗中显示出巨大潜力。
