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人参皂苷Rg1对博莱霉素诱导的大鼠肺纤维化的保护作用:小窝蛋白-1和转化生长因子-β1信号通路的参与

Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway.

作者信息

Zhan Heqin, Huang Feng, Ma Wenzhuo, Zhao Zhenghang, Zhang Haifang, Zhang Chong

机构信息

Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center.

出版信息

Biol Pharm Bull. 2016;39(8):1284-92. doi: 10.1248/bpb.b16-00046.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and high mortality rate. Panax Notoginseng Saponins (PNS), extracted from Panax Notoginseng as a traditional Asian medicine, displayed a significant anti-fibrosis effect in liver and lung. However, whether Ginsenoside Rg1 (Rg1), an important and active ingredient of PNS, exerts anti-fibrotic activity on IPF still remain unclear. In this study, we investigated the effect of Rg1 on bleomycin-induced pulmonary fibrosis in rats. Bleomycin (5 mg/kg body weight) was intratracheally administrated to male rats. Rg1 (18, 36 and 72 mg/kg) was orally administered on the next day after bleomycin. Lungs were harvested at day 7 and 28 for the further experiments. Histological analysis revealed that bleomycin successfully induced pulmonary fibrosis, and that Rg1 restored the histological alteration of bleomycin-induced pulmonary fibrosis (PF), significantly decreased lung coefficient, scores of alveolitis, scores of PF as well as contents of alpha smooth muscle actin (α-SMA) and hydroxyproline (Hyp) in a dose-dependent manner in PF rats. Moreover, Rg1 increased the expression levels of Caveolin-1 (Cav-1) mRNA and protein, lowered the expression of transforming growth factor-β1 (TGF-β1) mRNA and protein in the lung tissues of PF rats. These data suggest that Rg1 exhibits protective effect against bleomycin-induced PF in rats, which is potentially associated with the down-regulation of TGF-β1 and up-regulation of Cav-1.

摘要

特发性肺纤维化(IPF)是一种预后不良、死亡率高的进行性疾病。三七总皂苷(PNS)是从传统亚洲药物三七中提取的,在肝脏和肺部显示出显著的抗纤维化作用。然而,PNS的重要活性成分人参皂苷Rg1(Rg1)是否对IPF发挥抗纤维化活性仍不清楚。在本研究中,我们研究了Rg1对博来霉素诱导的大鼠肺纤维化的影响。将博来霉素(5mg/kg体重)经气管内给予雄性大鼠。在博来霉素给药后的第二天口服给予Rg1(18、36和72mg/kg)。在第7天和第28天收获肺组织用于进一步实验。组织学分析显示,博来霉素成功诱导了肺纤维化,并且Rg1恢复了博来霉素诱导的肺纤维化(PF)的组织学改变,显著降低了PF大鼠的肺系数、肺泡炎评分、PF评分以及α平滑肌肌动蛋白(α-SMA)和羟脯氨酸(Hyp)的含量,且呈剂量依赖性。此外,Rg1增加了小窝蛋白-1(Cav-1)mRNA和蛋白的表达水平,降低了PF大鼠肺组织中转化生长因子-β1(TGF-β1)mRNA和蛋白的表达。这些数据表明,Rg1对博来霉素诱导的大鼠PF具有保护作用,这可能与TGF-β1的下调和Cav-1的上调有关。

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