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五味子丙素对肺纤维化中胶原行为的抑制作用。

Inhibitory effects of Schisandrin C on collagen behavior in pulmonary fibrosis.

机构信息

Department of Molecular Biology Test Technique, College of Medical Technology, Beihua University, No. 3999 Binjiang East Road, Fengman District, Jilin, 132013, China.

Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, China.

出版信息

Sci Rep. 2023 Aug 18;13(1):13475. doi: 10.1038/s41598-023-40631-6.

DOI:10.1038/s41598-023-40631-6
PMID:37596361
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10439186/
Abstract

Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of α-SMA, FN, MMP2, MMP9, TIMP1 and collagen proteins such as Col 1A1, and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.

摘要

肺纤维化（PF）是一种严重的进行性纤维化疾病，其特征是细胞外基质（ECM）过度积累，从而导致肺组织变硬。赖氨酰氧化酶（LOX）是一种通过催化胶原蛋白交联参与纤维化的酶。研究发现，五味子的成分改善了博莱霉素（BLM）诱导的 PF，但尚不清楚五味子的抗 PF 是否与 LOX 有关。在这项研究中，我们建立了包括 BLM 刺激的小鼠模型和 TGF-β诱导的 HFL1 细胞模型在内的 PF 模型，以评估五味子醇 C（Sch C）对 PF 的抑制作用。我们观察到 Sch C 处理组与对照组相比，肺指数降低。Sch C 处理组的 ECM 积累明显减少，α-SMA、FN、MMP2、MMP9、TIMP1 和 Col 1A1、Col 3A1 等胶原蛋白的表达降低。此外，与 MOD 组相比，Sch C 处理后小鼠肺组织中 LOX 的表达有效降低。体外抑制作用与体内一致。机制研究表明，Sch C 显著抑制了 TGF-β/Smad2/3 和 TNF-α/JNK 信号通路。总之，我们的数据表明 Sch C 显著改善了体内和体外的 PF，这可能通过减少 ECM 沉积和抑制 LOX 的产生发挥重要作用。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/9d6f08597f71/41598_2023_40631_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/7389d378b7a3/41598_2023_40631_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/72b7e32cced8/41598_2023_40631_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/829f4d44f90a/41598_2023_40631_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/962a0428f489/41598_2023_40631_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/5d4e48310753/41598_2023_40631_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/9baab8553896/41598_2023_40631_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/263dc6779ac4/41598_2023_40631_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/433bbac859c6/41598_2023_40631_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d5f/10439186/edec80a41b9b/41598_2023_40631_Fig11_HTML.jpg

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