Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
J Nutr Biochem. 2014 Jun;25(6):592-9. doi: 10.1016/j.jnutbio.2014.01.010. Epub 2014 Mar 6.
Pro-inflammatory cytokines play a critical role in many models of liver injury. In addition, aspartate (Asp) plays an important role in many biological and physiological processes including liver physiology. We hypothesized that Asp could alleviate lipopolysaccharide (LPS)-induced liver injury. Forty-eight weanling pigs were assigned to four treatments including: (1) non-challenged control; (2) LPS challenged control; (3) LPS+0.5% Asp; (4) LPS+1.0% Asp. After 20-d feeding with control (0% Asp), 0.5% or 1.0% Asp supplemented diets, pigs were injected with saline or LPS. At 4 (early phase) and 24 h (late phase) post-injection, blood and liver samples were obtained. Asp attenuated liver injury indicated by reduced serum aspartate aminotransferase activity and increased ratio of serum alanine aminotransferase and aspartate aminotransferase at 24 h, and less severe histological liver damage induced by LPS challenge at 4 or 24 h. In addition, Asp supplementation to LPS challenged pigs decreased mRNA expressions of tumor necrosis factor (TNF)-α and cyclooxygenase-2 linearly and quadratically at 4 h, and increased mRNA expressions of these pro-inflammatory mediators linearly and quadratically at 24 h. Finally, Asp decreased mRNA expression of toll-like receptor 4 (TLR4) signaling related genes (TLR4, myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNF-α receptor-associated factor (6), nucleotide-binding oligomerization domain protein (NOD) signaling related genes (NOD1, NOD2 and receptor-interacting serine/threonine-protein kinase 2) and nuclear factor-κB p65 linearly or quadratically at 4 h. However, Asp increased mRNA expressions of these signaling molecules linearly or quadratically at 24 h. These results indicate that, at early and late phases of LPS challenge, Asp exerts opposite regulatory effects on mRNA expression of hepatic pro-inflammatory cytokines and TLR4 and NOD signalling related genes, and improves liver integrity.
促炎细胞因子在许多肝损伤模型中起着关键作用。此外，天冬氨酸（Asp）在许多生物学和生理过程中发挥重要作用，包括肝脏生理学。我们假设 Asp 可以减轻脂多糖（LPS）诱导的肝损伤。将 48 头断奶仔猪分为 4 种处理，包括：（1）未受挑战的对照组；（2）LPS 挑战对照组；（3）LPS+0.5%Asp；（4）LPS+1.0%Asp。用对照（0%Asp）、0.5%或 1.0%Asp 补充饲料喂养 20 天后，给猪注射盐水或 LPS。在注射后 4（早期）和 24 小时（晚期），采集血液和肝脏样本。Asp 可减轻 LPS 刺激引起的肝损伤，表现为血清天冬氨酸氨基转移酶活性降低，24 小时时血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶比值升高，4 或 24 小时时组织学肝损伤程度较轻。此外，Asp 补充 LPS 刺激的仔猪可使肿瘤坏死因子（TNF）-α 和环氧化酶-2 的 mRNA 表达在 4 小时时呈线性和二次递减，在 24 小时时呈线性和二次递增。最后，Asp 可使 TLR4 信号相关基因（TLR4、髓样分化因子 88、IL-1 受体相关激酶 1、TNF-α 受体相关因子（6）、核苷酸结合寡聚化结构域蛋白（NOD）信号相关基因（NOD1、NOD2 和受体相互作用丝氨酸/苏氨酸蛋白激酶 2）和核因子-κB p65 的 mRNA 表达在 4 小时时呈线性或二次递减。然而，Asp 可使这些信号分子的 mRNA 表达在 24 小时时呈线性或二次递增。这些结果表明，在 LPS 刺激的早期和晚期，Asp 对肝内促炎细胞因子和 TLR4 和 NOD 信号相关基因的 mRNA 表达产生相反的调节作用，并改善了肝完整性。
