College of Veterinary Medicine , Nanjing Agricultural University , Nanjing 210095 , P. R. China.
College of Animal Science and Technology , Nanjing Agricultural University , Nanjing 210095 , P. R. China.
J Agric Food Chem. 2018 Jun 27;66(25):6281-6290. doi: 10.1021/acs.jafc.8b01439. Epub 2018 Jun 14.
This study aimed to evaluate whether sodium butyrate (SB) attenuates the hepatic response to LPS-induced inflammation in bovine hepatocytes. Hepatocytes isolated from cows at ∼160 days in milk (DIM) were exposed to 0.5 mmol/L SB for 18 h as pretreatment. Cells pretreated with SB were used for the SB group, and those subjected to 4 μg/mL lipopolysaccharide (LPS) challenge for 6 h were used for the lipopolysaccharide pretreated with SB (LSB) group. The LPS-challenged hepatocytes showed increases in TNF-α and IL-6 production in culture medium (37 ± 11, P < 0.05); these increases were attenuated by pretreatment with SB in the LSB group (267 ± 4, P < 0.05). Compared to that in LPS-treated cells, the phospho-p65 and phospho-IκBα protein expression and nuclear translocation were suppressed when SB was added. Genes ( SREBP1c, SCD1, and DGAT1) and proteins (SREBP1c and SCD1) related to fatty acid metabolism were upregulated in LSB cells compared to those in LPS-treated cells ( P < 0.05). The ratios of phospho-AMPKα to AMPKα (0.32 ± 0.03 vs 0.70 ± 0.07) and phospho-ACCα to ACCα were decreased (0.81 ± 0.06 vs 2.06 ± 0.16) ( P < 0.05) in the LSB group. SB pretreatment reversed the histone H3 deacetylation that was increased by LPS stimulation in bovine hepatocytes (0.54 ± 0.02 vs 1.27 ± 0.11, P < 0.05). Our results suggest that SB pretreatment suppresses the hepatocyte changes that occur during the LPS-induced inflammatory response, which is accompanied by enhanced fatty acid synthesis, downregulated fatty acid oxidation, and histone H3 deacetylation, thus neutralizing the negative effects of infection.
本研究旨在评估丁酸钠（SB）是否能减轻牛肝细胞中 LPS 诱导的炎症反应。从约 160 天哺乳期奶牛中分离的肝细胞用 0.5mmol/L SB 预处理 18 小时。用 SB 预处理的细胞用于 SB 组，用 4μg/ml 脂多糖（LPS）刺激 6 小时的细胞用于 LPS 预处理的 SB（LSB）组。LPS 刺激的肝细胞在培养物中产生 TNF-α和 IL-6 的增加（37±11，P<0.05）；用 LSB 预处理减轻了 LPS 预处理细胞的增加（267±4，P<0.05）。与 LPS 处理的细胞相比，当添加 SB 时，磷酸化 p65 和磷酸化 IκBα 蛋白表达和核易位受到抑制。与 LPS 处理的细胞相比，LSB 细胞中与脂肪酸代谢相关的基因（SREBP1c、SCD1 和 DGAT1）和蛋白质（SREBP1c 和 SCD1）上调（P<0.05）。LSB 组磷酸化 AMPKα/AMPKα 的比值（0.32±0.03 对 0.70±0.07）和磷酸化 ACCα/ACCα 的比值（0.81±0.06 对 2.06±0.16）降低（P<0.05）。SB 预处理逆转了 LPS 刺激引起的牛肝细胞组蛋白 H3 去乙酰化（0.54±0.02 对 1.27±0.11，P<0.05）。我们的结果表明，SB 预处理抑制了 LPS 诱导的炎症反应中肝细胞的变化，同时增强了脂肪酸合成，下调了脂肪酸氧化和组蛋白 H3 去乙酰化，从而中和了感染的负面影响。
