Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice.
Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice.
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DOI：
10.1186/1465-9921-11-33
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发表时间：
2010-03-20
影响因子：
5.8
通讯作者：
Jiang T
中科院分区：
文献类型：
--
作者：
Ni YF;Wang J;Yan XL;Tian F;Zhao JB;Wang YJ;Jiang T
组蛋白去乙酰化酶（Histone deacetylase， HDAC）抑制剂由于能降低炎症细胞因子而具有抗炎作用，是一种很有前景的抗肿瘤药物。探讨HDAC抑制剂丁酸酯对脂多糖（LPS）致小鼠急性肺损伤（ALI）的保护作用。Balb/c小鼠经气管灌注LPS （1 mg/kg）诱导ALI。LPS给药1小时前，小鼠口服丁酸盐（10 mg/kg）。各组动物于LPS给药后的不同时间点处死。采用苏木精-伊红染色评价肺组织学变化，观察肺干/湿重比。采用酶联免疫吸附法（ELISA）测定支气管肺泡灌洗液（BALF）中白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的浓度以及肺组织匀浆中一氧化氮（NO）和髓过氧化物酶（MPO）活性的浓度。Western blot检测核因子(NF)-κB p65在细胞质和细胞核中的表达。丁酸盐预处理导致LPS显著减弱，引起明显的肺组织病理改变，肺泡出血，中性粒细胞浸润，MPO活性降低。肺湿/干重比，作为肺水肿的指标，丁酸盐给予降低。丁酸盐还能抑制TNF-α、IL-1β和NO的产生。此外，丁酸盐预处理能明显抑制细胞核中NF-κB p65的表达。丁酸盐对lps诱导的ALI具有保护作用，这可能与其抑制炎症细胞因子的产生和NF-κB的激活有关。
Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines. To investigate the protective effect of butyrate, a HDAC inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by intratracheally instillation of LPS (1 mg/kg). Before 1 hour of LPS administration, the mice received butyrate (10 mg/kg) orally. The animals in each group were sacrificed at different time point after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) and concentrations of nitric oxide (NO) and myeloperoxidase (MPO) activity in lung tissue homogenates were measured by enzyme-linked immunosorbent assay (ELISA). Expression of nuclear factor (NF)-κB p65 in cytoplasm and nucleus was determined by Western blot analysis respectively. Pretreatment with butyrate led to significant attenuation of LPS induced evident lung histopathological changes, alveolar hemorrhage, and neutrophils infiltration with evidence of reduced MPO activity. The lung wet/dry weight ratios, as an index of lung edema, were reduced by butyrate administration. Butyrate also repressed the production of TNF-α, IL-1β and NO. Furthermore, the expression of NF-κB p65 in nucleus was markedly suppressed by butyrate pretreatment. Butyrate had a protective effect on LPS-induced ALI, which may be related to its effect on suppression of inflammatory cytokines production and NF-κB activation.
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DOI：
10.1179/096805100101532108
发表时间：
2000-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Chakravortty, D;Koide, N;Yokochi, T
通讯作者：
Yokochi, T
影响因子：
24.5
作者：
Segain, JP;de la Blétière, DR;Galmiche, JP
通讯作者：
Galmiche, JP
DOI：
10.1164/ajrccm.164.10.2104013
发表时间：
2001-11-15
影响因子：
24.7
作者：
Park, WY;Goodman, RB;Martin, TR
通讯作者：
Martin, TR
影响因子：
5.8
作者：
Rahman, I
通讯作者：
Rahman, I
影响因子：
6.4
作者：
HAGUE, A;ELDER, DJE;PARASKEVA, C
通讯作者：
PARASKEVA, C