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丹酚酸 B 通过下调血管紧张素 II 信号通路减轻大鼠肝纤维化。

Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling.

机构信息

Institute of Liver Diseases, ShuGuang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Evid Based Complement Alternat Med. 2012;2012:160726. doi: 10.1155/2012/160726. Epub 2012 Nov 12.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c251/3518291/4321201bb759/ECAM2012-160726.001.jpg

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