Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-β Signaling Pathway.

Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-β Signaling Pathway.
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丹酚酸 B 通过抑制 TGF-β 信号通路减轻实验性肺纤维化

DOI:
10.1038/srep27610
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发表时间:
2016-06-09
期刊:
影响因子:
4.6
通讯作者:
Wang J
Wang J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu Q;Chu H;Ma Y;Wu T;Qian F;Ren X;Tu W;Zhou X;Jin L;Wu W;Wang J

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肺纤维化是一种进行性和致命的疾病。我们在前期研究中发现益气活血方对硬皮病这一典型的纤维化疾病有一定的疗效。本研究的目的是确定YQHX的治疗作用的关键成分,并检查其对肺纤维化的影响,包括其机制。荧光素酶报告基因检测结果表明,YQHX抗肝纤维化的主要成分是丹参。用博莱霉素灌注的肺纤维化小鼠模型进行的实验表明,丹参的主要成分丹参素B(SA B)通过抑制炎性细胞浸润、肺泡结构破坏和胶原沉积而具有强的抗炎和抗纤维化作用。此外,SAB抑制TGF-β诱导的MRC-5成纤维细胞的肌纤维母细胞分化和TGF-β介导的A549细胞的上皮-间充质转化,通过抑制Smad依赖性信号和Smad非依赖性MAPK途径。以上结果提示SM是YQHX抗肺纤维化的关键成分,而SM的主要成分SAB通过抑制TGF-β信号通路,在体内和体外均能减轻实验性肺纤维化。总之,这些结果表明,SAB有效地抑制肺纤维化。
Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti-fibrotic component of the YQHX wasSalviae miltiorrhiza(SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption and collagen deposition. Furthermore, SAB suppressed TGF-β-induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF-β-mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti-fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis bothin vivoandin vitroby inhibiting the TGF-β signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis.