Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China.
Sci Rep. 2019 Dec 10;9(1):18719. doi: 10.1038/s41598-019-54663-4.
Fuzhenghuayu (FZHY) is a compound extracted from natural plants. Its anti-fibrotic effect has been confirmed in experimental and clinical studies. However, precise effects and underlying mechanisms of FZHY in liver angiogenesis largely remain understood. In this study, we investigated the effects of FZHY on sinusoidal capillarization and angiogenesis with mice challenged for Carbon tetrachloride (CCl) and dimethylnitrosamine (DMN), in vitro human hepatic sinusoidal endothelial cells (HHSEC) and Human Umbilical Vein Endothelial Cell (HUVEC) 3D fibrin gel model. Besides its anti-fibrotic effect, FZHY ameliorated CCl and DMN-induced sinusoidal capillarization, angiogenesis and expression of angiogenesis-associated factors, i.e. CD31, VEGF, VEGF receptor II, phosphor-ERK and HIF-1α. Consistent with the findings based on animal models, inhibitory effects of FZHY on capillarization and angiogenesis were further confirmed in HHSEC and the HUVEC 3D fibrin gel model, respectively. These data suggest that FZHY ameliorates not only liver fibrosis but also vessel remodeling in experimental models. Therefore, FZHY might be a potentially useful drug to treat liver cirrhosis in clinical practice.
扶正化瘀(FZHY)是一种从天然植物中提取的化合物。其抗纤维化作用已在实验和临床研究中得到证实。然而,FZHY 在肝血管生成中的确切作用和潜在机制在很大程度上仍未被了解。在这项研究中,我们研究了 FZHY 对 CCl 和 DMN 刺激的小鼠、体外人肝窦内皮细胞(HHSEC)和人脐静脉内皮细胞(HUVEC)3D 纤维蛋白凝胶模型中的血管生成和血管生成相关因子(即 CD31、VEGF、VEGF 受体 II、磷酸化 ERK 和 HIF-1α)的影响。除了抗纤维化作用外,FZHY 还改善了 CCl 和 DMN 诱导的窦状毛细血管化、血管生成和血管生成相关因子的表达。与动物模型的研究结果一致,FZHY 对 HHSEC 和 HUVEC 3D 纤维蛋白凝胶模型中的毛细血管化和血管生成的抑制作用也得到了进一步证实。这些数据表明,FZHY 不仅能改善肝纤维化,还能改善实验模型中的血管重塑。因此,FZHY 可能是一种在临床实践中治疗肝硬化的潜在有效药物。