Institute of Liver Diseases, ShuGuang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Evid Based Complement Alternat Med. 2012;2012:160726. doi: 10.1155/2012/160726. Epub 2012 Nov 12.
The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs) in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) and α-smooth muscle actin (α-SMA) production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.
肾素-血管紧张素系统(RAS)在肝纤维化中起着重要作用。丹参素 B(Sal B)是丹参的水溶性成分之一,已被用于治疗肝纤维化,但尚不清楚 Sal B 的作用是否与血管紧张素 II(Ang II)信号通路有关。在本研究中,我们研究了 Sal B 对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化模型体内和 Ang II 刺激的肝星状细胞(HSCs)体外的影响,分别以培哚普利或氯沙坦作为对照药物。结果表明,Sal B 和培哚普利抑制大鼠肝纤维化,并降低纤维化肝脏中 Ang II 受体 1(AT1R)和 ERK 激活的表达。Sal B 和氯沙坦还抑制 Ang II 刺激的 HSC 激活,包括细胞增殖以及 I 型胶原 I(Col-I)和α-平滑肌肌动蛋白(α-SMA)的表达,降低转化生长因子β(TGF-β)的基因表达,并下调 AT1R 表达和 ERK 和 c-Jun 的磷酸化。总之,我们的结果表明,Sal B 可能通过下调 HSC 激活中的 Ang II 信号发挥抗肝纤维化作用。