Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
PLoS One. 2013 Jul 25;8(7):e70309. doi: 10.1371/journal.pone.0070309. Print 2013.
Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.
长期补充支链氨基酸（BCAA）与肝硬化患者的生存时间延长和肝细胞癌（HCC）发生频率降低有关。然而，这种关联的药物机制尚不清楚。我们研究了连续补充 BCAA 是否会增加暴露于纤维发生剂的大鼠的存活率，并影响肝脏中的铁积累、氧化应激、纤维化和糖异生。此外，还研究了 BCAA 对培养细胞中糖异生的影响。与未治疗的肝硬化大鼠相比，补充 BCAA 的晚期肝硬化大鼠的累积存活率有显著提高（P<0.05）。BCAA 补充延长的存活率与肝脏中铁含量、活性氧产生和纤维化减轻有关。此外，BCAA 通过 forkhead box protein O1 通路改善了肝脏中的葡萄糖代谢。BCAA 延长了肝硬化大鼠的生存时间，这可能是由于肝脏中铁积累、氧化应激和纤维化减少以及葡萄糖代谢改善的结果。
