Beijing You an Hospital, Capital Medical University, Beijing, China; Beijing Institute of Hepatology, Beijing, P.R. China.
Beijing You an Hospital, Capital Medical University, Beijing, China.
Ann Hepatol. 2019 Sep-Oct;18(5):757-764. doi: 10.1016/j.aohep.2019.03.007. Epub 2019 Jul 22.
Hypoxia-inducible factor-1α is critically involved in the pathogenesis of liver diseases. Its inhibitor genistein attenuated D-galactosamine (D-GalN)-induced liver damage. However, the role of genistein in acute-on-chronic liver failure (ACLF) is unclear. The influence of genistein on reactive oxygen species (ROS) and hepatocyte functions were evaluated in a rat model of ACLF.
Genistein [20mg/ (kg. day)]/coenzyme Q10 [10mg/ (kg. day)]/lipoic acid [20mg/ (kg. day)] was administered via the intra-gastric route daily for 6 weeks as co-treatment to the rats in the experimental groups. Then, 100μg/kg LPS combined with 0.5g/kg D-GalN was injected intraperitoneally to attack the rats.
Genistein significantly attenuated LPS/D-GalN-induced ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, reduced AST level in serum, whereas increased levels of ATP, ADP/O, and respiratory control ratio (RCR) in mitochondria. Genistein suppressed necrosis and ROS production.
These results suggested that genistein could protect against ACLF through inhibiting cellular ROS production and necrosis, improving RCR, and decreasing permeability transition pores in mitochondrial, which was similar as mitochondrial protective agent coenzyme Q10.
缺氧诱导因子-1α 在肝脏疾病的发病机制中起着至关重要的作用。其抑制剂染料木黄酮可减轻半乳糖胺（D-GalN）诱导的肝损伤。然而，染料木黄酮在慢加急性肝衰竭（ACLF）中的作用尚不清楚。本研究在 ACLF 大鼠模型中评估了染料木黄酮对活性氧（ROS）和肝细胞功能的影响。
通过灌胃途径每天给予染料木黄酮[20mg/（kg·天）] /辅酶 Q10[10mg/（kg·天）] /硫辛酸[20mg/（kg·天）]联合治疗实验组大鼠 6 周。然后，腹腔内注射 100μg/kg LPS 联合 0.5g/kg D-GalN 攻击大鼠。
染料木黄酮显著减轻了 LPS/D-GalN 诱导的 ACLF，表现为肝大体外观和组织病理学的改善，血清 AST 水平降低，而线粒体中 ATP、ADP/O 和呼吸控制比（RCR）水平升高。染料木黄酮抑制了坏死和 ROS 的产生。
这些结果表明，染料木黄酮通过抑制细胞 ROS 产生和坏死、提高 RCR 和减少线粒体通透性转换孔来保护 ACLF，这与线粒体保护剂辅酶 Q10 相似。
