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白藜芦醇通过 TGF-β/Smad/ERK 信号通路对肺纤维化的影响。

Effects of Resveratrol on Pulmonary Fibrosis via TGF-β/Smad/ERK Signaling Pathway.

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital, Hainan Medical University, Longhua, Haikou 570102, P. R. China.

Hainan Province Clinical Medical Center of Respiratory Disease, Longhua, Haikou 579199, P. R. China.

出版信息

Am J Chin Med. 2023;51(3):651-676. doi: 10.1142/S0192415X23500313. Epub 2023 Mar 9.

Abstract

Pulmonary fibrosis (PF) is a progressive pulmonary disease with no effective treatment and high mortality. Resveratrol has shown promising benefits in the treatment of PF. However, the probable efficacy and underlying mechanism of resveratrol in PF treatment remain unclear. This study investigates the intervention effects and potential mechanisms underpinning the treatment of PF with resveratrol. The histopathological analysis of lung tissues in PF rats showed that resveratrol improved collagen deposition and reduced inflammation. Resveratrol decreased the levels of collagen, glutathione, superoxide dismutase, myeloperoxidase, and hydroxyproline, lowered total anti-oxidant capacity, and suppressed the migration of TGF-[Formula: see text]1 and LPS-induced 3T6 fibroblasts. With resveratrol intervention, the protein and RNA expressions of TGF-[Formula: see text]1, a-SMA, Smad3/4, p-Smad3/4, CTGF, and p-ERK1/2 were markedly downregulated. Similarly, the protein and RNA expression levels of Col-1 and Col-3 were significantly downregulated. However, Smad7 and ERK1/2 were evidently upregulated. The protein and mRNA expression levels of TGF-[Formula: see text], Smad, and p-ERK correlated positively with the lung index, while the protein and mRNA expression levels of ERK correlated negatively with the lung index. These results reveal that resveratrol may have therapeutic effects on PF by reducing collagen deposition, oxidation, and inflammation. The mechanism is associated with the regulation of the TGF-[Formula: see text]/Smad/ERK signaling pathway.

摘要

肺纤维化(PF)是一种进展性肺部疾病,目前尚无有效治疗方法,死亡率高。白藜芦醇在 PF 治疗中显示出良好的疗效。然而,白藜芦醇治疗 PF 的可能疗效和潜在机制尚不清楚。本研究旨在探讨白藜芦醇干预 PF 的疗效及其潜在机制。PF 大鼠肺组织的组织病理学分析表明,白藜芦醇可改善胶原蛋白沉积并减轻炎症。白藜芦醇降低了胶原蛋白、谷胱甘肽、超氧化物歧化酶、髓过氧化物酶和羟脯氨酸的水平,降低了总抗氧化能力,并抑制了 TGF-β1 和 LPS 诱导的 3T6 成纤维细胞的迁移。白藜芦醇干预后,TGF-β1、α-SMA、Smad3/4、p-Smad3/4、CTGF 和 p-ERK1/2 的蛋白和 RNA 表达明显下调。同样,Col-1 和 Col-3 的蛋白和 RNA 表达水平也明显下调。然而,Smad7 和 ERK1/2 明显上调。TGF-β、Smad 和 p-ERK 的蛋白和 mRNA 表达水平与肺指数呈正相关,而 ERK 的蛋白和 mRNA 表达水平与肺指数呈负相关。这些结果表明,白藜芦醇可能通过减少胶原蛋白沉积、氧化和炎症对 PF 具有治疗作用。其机制与 TGF-β/Smad/ERK 信号通路的调节有关。

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