Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Tohoku J Exp Med. 2010 Jun;221(2):151-9. doi: 10.1620/tjem.221.151.
It has been reported that treatment with branched chain amino acids (BCAAs) increases the survival rates in cirrhotic patients. In this study, we investigated the effect of L-valine, one of BCAAs, on liver fibrosis in rat. To induce liver fibrosis, male Wistar rats were injected carbon tetrachloride (CCl(4)) intraperitoneally (2.0 mL/kg) twice a week for 12 weeks. The rats (seven to fifteen rats for each group) were then administered 1.688 g/kg/day of L-valine intravenously for 7 days or 10% amino acid preparation that provided the same amount of nitrogen. Seven days after the last administration, blood platelet counts and bone marrow megakaryocyte counts were significantly higher in the valine group than in the control group (131.2 +/- 38.3 vs. 106.3 +/- 14.5 x 10(4)/microL, p = 0.04; 18.0 +/- 2.1 vs. 13.5 +/- 2.2 per field, p < 0.01, respectively). Importantly, the mRNA level of thrombopoietin, a key regulator of thrombopoiesis, was significantly higher in the liver of the valine group than the control group. Furthermore, hepatic fibrosis was significantly reduced in the valine group, and the mRNA levels of factors associated with liver fibrosis such as procollagen alpha1(III), transforming growth factor-beta1 and connective tissue growth factor were significantly lower in the liver of the valine group 10 days after the last administration. These results indicate that L-valine treatment ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to CCl(4). Therefore, L-valine supplementation may be helpful for patients with liver cirrhosis.
据报道，支链氨基酸（BCAAs）的治疗可提高肝硬化患者的存活率。在这项研究中，我们研究了 L-缬氨酸（BCAA 之一）对大鼠肝纤维化的影响。为了诱导肝纤维化，雄性 Wistar 大鼠腹膜内注射四氯化碳（CCl 4 ）（2.0 mL/kg），每周两次，共 12 周。然后，将大鼠（每组 7 至 15 只）静脉内给予 1.688 g/kg/天的 L-缬氨酸 7 天或提供相同氮量的 10%氨基酸制剂。最后一次给药后 7 天，缬氨酸组的血小板计数和骨髓巨核细胞计数明显高于对照组（131.2 +/- 38.3 对 106.3 +/- 14.5 x 10 4 / μL，p = 0.04；18.0 +/- 2.1 对 13.5 +/- 2.2 个/视野，分别为 p < 0.01）。重要的是，肝中关键的血小板生成调节剂——血小板生成素的 mRNA 水平在缬氨酸组明显高于对照组。此外，缬氨酸组肝纤维化明显减轻，最后一次给药 10 天后，与肝纤维化相关的因子如前胶原 alpha1（III）、转化生长因子-β1 和结缔组织生长因子的 mRNA 水平在肝中明显降低。这些结果表明，L-缬氨酸治疗可改善 CCl 4 暴露大鼠的肝纤维化并恢复血小板生成。因此，L-缬氨酸补充可能对肝硬化患者有帮助。
