Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, People's Republic of China.
Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
Br J Nutr. 2014 Jan 14;111(1):46-54. doi: 10.1017/S0007114513002171. Epub 2013 Jul 8.
The present study was carried out to determine whether N-acetylcysteine (NAC) could modulate liver injury in a lipopolysaccharide (LPS)-challenged piglet model. For this purpose, eighteen piglets were randomly assigned to the control, LPS or NAC group. Piglets in the control and LPS groups were fed a basal diet, whereas those in the NAC group were fed the basal diet supplemented with 500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS- and NAC-treated piglets were intraperitoneally administered LPS (100 μg/kg body weight), while the control group was administered the same volume of saline. On day 20 of the trial, blood samples were obtained 3 h after LPS or saline injection. On day 21, the piglets were killed to collect liver samples. Dietary NAC supplementation attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, in the LPS-challenged piglets, the activities of alanine aminotransferase and aspartate aminotransferase and the concentrations of H2O2, TNF-α, IL-6 and PGE2 were dramatically increased in the plasma and the activity of superoxide dismutase in the plasma and that of glutathione peroxidase in the liver were significantly decreased. The LPS challenge also increased the concentration of AMP and the ratio of AMP:ATP, but decreased adenylate energy charges and the levels of ATP and ADP. These adverse effects of the LPS challenge were ameliorated by NAC supplementation. Moreover, NAC inhibited the LPS-induced increases in the abundance of liver heat shock protein 70 and NF-κB proteins. In conclusion, these results suggest that dietary NAC supplementation alleviates LPS-induced liver injury by reducing the secretion of pro-inflammatory cytokines, increasing the antioxidative capacity and improving energy metabolism.
本研究旨在探讨 N-乙酰半胱氨酸(NAC)是否可以调节脂多糖(LPS)刺激的仔猪模型中的肝损伤。为此,将 18 头仔猪随机分为对照组、LPS 组或 NAC 组。对照组和 LPS 组仔猪饲喂基础日粮,而 NAC 组仔猪则饲喂补充 500mg/kg NAC 的基础日粮。试验第 10、13 和 20 天,LPS 和 NAC 处理的仔猪分别经腹腔注射 LPS(100μg/kg 体重),对照组仔猪则注射相同体积的生理盐水。试验第 20 天,LPS 或生理盐水注射后 3 小时采集血样。试验第 21 天,处死仔猪采集肝脏样本。饲粮 NAC 补充可减轻 LPS 诱导的肝组织形态学异常。与对照组相比,在 LPS 刺激的仔猪中,血浆中转氨酶(ALT 和 AST)活性以及 H2O2、TNF-α、IL-6 和 PGE2 浓度显著升高,血浆中超氧化物歧化酶活性以及肝组织中谷胱甘肽过氧化物酶活性显著降低。LPS 刺激还增加了 AMP 浓度和 AMP:ATP 比值,但降低了腺苷酸能量电荷以及 ATP 和 ADP 水平。NAC 补充可改善 LPS 刺激引起的这些不利影响。此外,NAC 抑制了 LPS 诱导的肝热休克蛋白 70 和 NF-κB 蛋白丰度的增加。综上所述,这些结果表明,饲粮 NAC 补充通过减少促炎细胞因子的分泌、增加抗氧化能力和改善能量代谢来减轻 LPS 诱导的肝损伤。