Valproic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice
Valproic Acid Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice
复制标题
DOI：
10.1007/s10753-013-9686-z
复制
发表时间：
2013-12-01
期刊：
影响因子：
5.1
通讯作者：
Yang, Jian-jun
中科院分区：
文献类型：
--
作者：
Ji, Mu-huo;Li, Guo-min;Yang, Jian-jun
丙戊酸 (VPA) 已被证明在包括感染性休克在内的一系列疾病中发挥抗炎和抗氧化作用。然而，VPA 对脂多糖 (LPS) 诱导的急性肺损伤 (ALI) 的影响仍不清楚。我们发现，VPA 预处理可减轻 LPS 诱导的 ALI，肺组织组织学评分、髓过氧化物酶活性和湿干重比的降低就证明了这一点。伴随着肺组织中核因子kappa B (NF-kappa B) p65、一氧化氮和诱导型一氧化氮合酶的下调，以及支气管肺泡灌洗液中肿瘤坏死因子α和白介素-1β水平的降低。此外，VPA 降低了核组蛋白脱乙酰酶 (HDAC)3 的表达，而增加了细胞质 HDAC3 的表达。我们的结果表明，VPA 可能通过依赖于 HDAC3 重新分布的机制抑制 NF-κ B 激活，从而减轻 LPS 诱导的 ALI。
Valproic acid (VPA) has been shown to exert anti-inflammatory and antioxidant effects in a range of diseases including septic shock. However, the effects of VPA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. We found that VPA pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the downregulated nuclear factor kappa B (NF-kappa B) p65, nitric oxide, and inducible nitric oxide synthase in the lung tissues and the decreased levels of tumor necrosis factor alpha and interleukin-1 beta in the bronchoalveolar lavage fluid. Furthermore, VPA reduced the nuclear histone deacetylase (HDAC)3 expression whereas increased the cytoplasmic HDAC3 expression. Our results suggested that VPA attenuates the LPS-induced ALI via inhibiting the NF-kappa B activation probably through a mechanism depending on HDAC3 redistribution.