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

Protective Effect of Ginsenoside Rg1 on Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of Caveolin-1 and TGF-β1 Signal Pathway
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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:Caveolin-1 和 TGF-β1 信号通路的参与。

DOI:
10.1248/bpb.b16-00046
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发表时间:
2016-08-01
影响因子:
2
通讯作者:
Zhang, Chong
Zhang, Chong
中科院分区:
医学4区
文献类型:
--
作者:
Zhan, Heqin;Huang, Feng;Zhang, Chong

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特发性肺纤维化(IPF)是一种进展性疾病,预后差,死亡率高。三七总皂苷(PNS)是从亚洲传统药材三七中提取的有效成分,对肝、肺具有显著的抗纤维化作用。然而,三七总皂苷的重要活性成分人参皂苷Rg1(Rg1)对IPF是否具有抗纤维化作用仍不清楚。在本研究中,我们观察了Rg1对博莱霉素诱导的大鼠肺纤维化的影响。雄性大鼠气管内注射博莱霉素(5 mg/kg体重)。博莱霉素后次日灌胃Rg1(18、36、72 mg/kg)。分别于第7天和第28天取肺进行进一步的实验。组织学分析表明,博莱霉素能成功地诱导肺纤维化,Rg1可剂量依赖性地恢复博莱霉素性肺纤维化大鼠的肺系数、肺泡炎评分、肺纤维化评分以及α-平滑肌肌动蛋白(α-SMA)和羟脯氨酸(Hyp)含量。此外,Rg1还能上调肺纤维化大鼠肺组织小窝蛋白-1(Cav-1)的表达水平,降低转化生长因子-β1(TGF-β1)的mRNA和蛋白表达。提示RGL对博莱霉素性肺纤维化大鼠具有保护作用,其机制可能与下调转化生长因子-β1和上调Cav-1有关。
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 (alpha-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-beta (TGF-beta 1) mRNA and protein in the lung tissues of PF rats. These data suggest that Rgl exhibits protective effect against bleomycin-induced PF in rats, which is potentially associated with the down-regulation of TGF-beta 1 and up regulation of Cav-1.