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五味子通过抑制 M2 型巨噬细胞极化抑制博来霉素诱导的大鼠特发性肺纤维化。

Schisandra Inhibit Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats via Suppressing M2 Macrophage Polarization.

机构信息

Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

Liberal and Art College, New Jersey Institute of Technology, Newark 07102, USA.

出版信息

Biomed Res Int. 2020 Aug 20;2020:5137349. doi: 10.1155/2020/5137349. eCollection 2020.

Abstract

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause and limited to the lungs. (Wuweizi, Schisandra) is commonly used traditional Chinese medicines (TCM) for the treatment of pulmonary fibrosis, bronchitis, and other lung diseases in China. In this study, we investigated the therapeutic effect of Schisandra on IPF which is induced by bleomycin (BLM) in rats and the inhibition of alternatively activated macrophage (M2) polarization. Bleomycin-induced pulmonary fibrosis was used as a model for IPF, and rats were given drug interventions for 7 and 28 days to evaluate the role of Schisandra in the early oxidative phase and late fibrotic phases of BLM-induced pulmonary injury. The data showed that Schisandra exerted protective effects on BLM-induced pulmonary injury in two phases, which were improving inflammatory cell infiltration and severe damages of lung architectures and decreasing markers of M2 subtype. In order to prove the inhibitory effect of Schisandra on M2 polarization, in vitro experiments, we found that Schisandra downregulated the M2 ratio, which confirmed that the polarization of M2 was suppressed. Moreover, Schisandra blocked TGF-1 signaling in AMs by reducing the levels of Smad3 and Smad4; meanwhile, the upregulation of Smad7 by Schisandra also promoted the effect of inhibition on the TGF-1/Smad pathway. These results demonstrate that suppression of M2 polarization by Schisandra is associated with the development of IPF in rats.

摘要

特发性肺纤维化(IPF)被定义为一种原因不明且仅局限于肺部的慢性、进行性纤维性间质性肺炎的特殊形式。五味子是中国治疗肺纤维化、支气管炎和其他肺部疾病的常用中药。本研究探讨了五味子对博莱霉素(BLM)诱导的大鼠肺纤维化的治疗作用及其对交替激活的巨噬细胞(M2)极化的抑制作用。BLM 诱导的肺纤维化被用作 IPF 的模型,给予大鼠药物干预 7 天和 28 天,以评估五味子在 BLM 诱导的肺损伤的早期氧化期和晚期纤维化期的作用。结果表明,五味子在两个阶段对 BLM 诱导的肺损伤均具有保护作用,即改善炎症细胞浸润和严重的肺结构损伤,并降低 M2 亚型的标志物。为了证明五味子对 M2 极化的抑制作用,我们进行了体外实验,发现五味子下调了 M2 比值,证实了 M2 极化受到抑制。此外,五味子通过降低 Smad3 和 Smad4 的水平阻断 AM 中的 TGF-β1 信号通路;同时,五味子上调 Smad7 也促进了对 TGF-β1/Smad 通路的抑制作用。这些结果表明,五味子抑制 M2 极化与大鼠 IPF 的发展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50bd/7455820/32f17dad97be/BMRI2020-5137349.001.jpg

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