白藜芦醇通过调节SIRT3/TGF-β1/Smad信号通路改善肌硬膜桥的病理性纤维化。

Resveratrol ameliorates pathological fibrosis of the myodural bridge by regulating the SIRT3/TGF-β1/Smad pathway.

作者信息

Qin Tao, Song Xue, Shao Qing, Zhang Jianfei, Sui Hongjin

机构信息

Department of Anatomy, Dalian Medical University, 9 West Section, Lushun South Road, Dalian, Liaoning Province, 116044, China.

Graduate School, Dalian Medical University, 9 West Section, Lushun South Road, Dalian, Liaoning Province, 116044, China.

出版信息

Heliyon. 2024 Jul 19;10(15):e34974. doi: 10.1016/j.heliyon.2024.e34974. eCollection 2024 Aug 15.

DOI:10.1016/j.heliyon.2024.e34974

PMID:39145011

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11320322/

Abstract

PURPOSE

Pathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms.

METHODS

Genes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-β1 (TGF-β1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ.

RESULTS

Through network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-β1/Smad pathway.

CONCLUSION

Resveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB and may be considered a novel therapeutic strategy.

摘要

目的

肌硬膜桥（MDB）的病理性纤维化会影响脑脊液循环。然而，目前尚无最佳药物治疗方法。我们旨在探讨白藜芦醇对博来霉素诱导的MDB病理性纤维化的抗纤维化作用及其潜在机制。

方法

使用网络药理学确定白藜芦醇潜在靶点的共同基因，从GeneCards数据库获取与肌肉和肌腱纤维化相关的基因，并使用Venny确定与MDB发育相关的基因。这些基因被认为是博来霉素诱导的MDB病理性纤维化中白藜芦醇治疗的潜在靶点，并采用生物信息学方法进行注释。我们使用定量实时聚合酶链反应（qRT-PCR）验证了交集基因，并进行分子对接分析以计算靶基因与白藜芦醇之间的结合活性。采用苏木精-伊红染色和Masson染色检测白藜芦醇治疗后博来霉素诱导的MDB纤维化的形态学变化。我们使用qRT-PCR和免疫组织化学评估沉默调节蛋白3（SIRT3）/转化生长因子-β1（TGF-β1）/Smad通路以及促纤维化标志物α-平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原蛋白的表达。

结果

通过网络药理学和生物信息学分析，我们确定了四个核心交集基因，并使用qRT-PCR验证了SIRT3的表达。分子对接分析表明白藜芦醇与SIRT3具有良好的结合亲和力。白藜芦醇通过抑制成纤维细胞活化和过度的胶原纤维沉积，改善了博来霉素诱导的MDB病理性纤维化中的形态异常。白藜芦醇通过调节SIRT3/TGF-β1/Smad通路发挥其抗纤维化作用。