AD-1对脂多糖介导的L929细胞成纤维细胞损伤和博来霉素诱导的小鼠肺纤维化的抗纤维化作用,Food & Function

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AD-1对脂多糖介导的L929细胞成纤维细胞损伤和博来霉素诱导的小鼠肺纤维化的抗纤维化作用
Food & Function ( IF 5.1 ) Pub Date : 2022-06-07 , DOI: 10.1039/d1fo04212b
Tao Li _{1,

2} , Yu Chen ₁ , Yuan Li _{1,

3} , Gang Chen ₁ , Yuqing Zhao ₂ , Guangyue Su ₁

Affiliation

20( R )-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH ₃ –PPD, AD-1) 是一种从三七中分离出来的达玛烷人参皂苷。本研究旨在探索其在体外和体内的抗肺纤维化（PF）作用。L929细胞用10 μg mL ^-1脂多糖（LPS）处理体外建立PF模型，小鼠用3.5 mg kg ^-1博来霉素（BLM）气管插管建立体内PF模型用于研究抗PF作用及其潜在机制。结果表明AD-1降低了LPS诱导的L929的损伤、细胞外基质（ECM）积累和α-平滑肌肌动蛋白（α-SMA）蛋白表达水平。口服AD-1可下调白细胞介素（如IL-1β、IL-6和IL-18）的表达，增加超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的表达，降低肺系数和肺组织含量。羟脯氨酸 (HYP)，并介导小鼠肺组织中 Bax/Bcl-2 蛋白比例和 P-p53、β-catenin 和 SIRT3 的表达。此外，AD-1 抑制 TGF-β1、TIMP-1 和 α-SMA 的表达水平，并减少 PF 小鼠肺组织中的炎症细胞浸润和胶原蛋白沉积。这些结果表明AD-1可以减轻PF其机制可能与减少 ECM 沉积和炎症、增强抗氧化能力、介导肺细胞凋亡和 TGF-β1/TIMP-1/α-SMA 信号通路有关。，为PF的康复治疗提供理论依据。

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Antifibrotic effect of AD-1 on lipopolysaccharide-mediated fibroblast injury in L929 cells and bleomycin-induced pulmonary fibrosis in mice

20(R)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH₃–PPD, AD-1) is a dammarane ginsenoside that is isolated from Panax notoginseng. The present study aimed to explore its anti-pulmonary fibrosis (PF) effect in vitro and in vivo. L929 cells were treated with 10 μg mL⁻¹ lipopolysaccharide (LPS) to establish a PF model in vitro and mice were administered with 3.5 mg kg⁻¹ bleomycin (BLM) by endotracheal intubation to establish a PF model in vivo for investigating the anti-PF effect and its potential mechanism. The results demonstrated that AD-1 reduced the injury, extracellular matrix (ECM) buildup and α-smooth muscle actin (α-SMA) protein expression levels of L929 induced by LPS. Oral administration of AD-1 downregulated the expression of interleukins (such as IL-1β, IL-6 and IL-18), increased the expression of superoxide dismutase (SOD) and glutathione (GSH), reduced the lung coefficient and the content of hydroxyproline (HYP), and mediated the Bax/Bcl-2 protein ratio and P-p53, β-catenin and SIRT3 expression in the lung tissue of mice. Furthermore, AD-1 inhibited the expression levels of TGF-β1, TIMP-1 and α-SMA and reduced inflammatory cell infiltration and collagen deposition in the lung tissue of PF mice. These results indicated that AD-1 could alleviate PF both in vitro and in vivo, and the underlying mechanism may be related to the decrease in ECM deposition and inflammation, the enhancement of antioxidant capacity, and the mediation of lung cell apoptosis and the TGF-β1/TIMP-1/α-SMA signaling pathway, which provide a theoretical basis for the rehabilitation treatment of PF.

更新日期：2022-06-07

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