Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
J Ethnopharmacol. 2013 Oct 7;149(3):825-32. doi: 10.1016/j.jep.2013.08.017. Epub 2013 Aug 22.
In the theory of traditional Chinese medicine, pulmonary fibrosis (PF) belongs to pulmonary arthralgia, which means blood stasis in lung tissue. The roots of Paeonia lactiflora Pall are usually used to relieve the symptoms of this disease by promoting blood circulation and removing blood stasis. Paeoniflorin, the main active ingredient of P. lactiflora, may have anti-PF potential.
This study aimed to investigate the effects and underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice.
The PF model was established in mice by an intratracheal instillation of BLM. Paeoniflorin (25, 50, 100mg/kg) and prednisone (6mg/kg), as a positive control, were orally administered for consecutive 21 days. Histopathological changes were evaluated by hematoxylin and eosin stain and Masson's trichrome stain. The content of hydroxyproline was detected by using kits. The contents of type I collagen, TGF-β1 and IFN-γ were detected by ELISA. The levels of α-SMA, Smad4, Smad7 and the phosphorylations of Smad2/3 were detected by western blot. The mRNA expressions of MMP-1 and TIMP-1 were detected by RT-PCR.
In mice treated with BLM, paeoniflorin (50mg/kg) significantly prolonged the survival periods, attenuated infiltration of inflammatory cells, interstitial fibrosis, and deposition of extracellular matrix in lung tissues. It also decreased the contents of hydroxyproline (a marker of collagens), type I collagen and α-SMA (an indicator of myofibroblasts) in lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-β1, Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-γ. But, it only slightly affected mRNA expressions of MMP-1 and TIMP-1 in lung tissues of mice.
Paeoniflorin attenuates PF by suppressing type I collagen synthesis via inhibiting the activation of TGF-β/Smad pathway and increasing the expression of IFN-γ.
在中医理论中，肺纤维化（PF）属于肺痹，即肺组织血瘀。白芍的根通常用于通过促进血液循环和消除血瘀来缓解这种疾病的症状。白芍的主要活性成分芍药苷可能具有抗 PF 潜力。
本研究旨在探讨芍药苷对博莱霉素（BLM）诱导的小鼠 PF 的作用及作用机制。
通过气管内滴注 BLM 建立 PF 模型。芍药苷（25、50、100mg/kg）和泼尼松（6mg/kg）作为阳性对照，连续口服 21 天。苏木精和伊红染色和 Masson 三色染色评估组织病理学变化。羟脯氨酸含量采用试剂盒检测。ELISA 法检测 I 型胶原、TGF-β1 和 IFN-γ含量。Western blot 检测 α-SMA、Smad4、Smad7 水平及 Smad2/3 磷酸化。RT-PCR 检测 MMP-1 和 TIMP-1 的 mRNA 表达。
在 BLM 处理的小鼠中，芍药苷（50mg/kg）显著延长了生存时间，减轻了炎症细胞浸润、间质纤维化和细胞外基质在肺组织中的沉积。它还降低了羟脯氨酸（胶原蛋白的标志物）、I 型胶原和 α-SMA（肌成纤维细胞的指标）在小鼠肺组织中的含量。芍药苷下调 TGF-β1、Smad4 和 Smad2/3 的磷酸化，上调 Smad7 的表达。此外，芍药苷增加了 IFN-γ的含量。但是，它只对小鼠肺组织中 MMP-1 和 TIMP-1 的 mRNA 表达有轻微影响。
芍药苷通过抑制 TGF-β/Smad 通路的激活和增加 IFN-γ的表达来抑制 I 型胶原的合成，从而减轻 PF。
