目的:杜松子酮具有多种生物活性,本研究的目的是研究白术碱对TGF-β1诱导的细胞模型增殖的影响,及其减轻博莱霉素刺激的小鼠肺纤维化的能力。
方法:体外,我们评估了菊酯碱(350、550和750µM)对TGF-β1(10μg/L)刺激的细胞增殖的影响,以及α-SMA活力等参数,人纤连蛋白,胶原蛋白,和细胞中的羟脯氨酸水平。在体内,我们分析了炎症,羟脯氨酸,小鼠肺中的胶原蛋白活性和代谢组学。此外,对TGF-β/SMAD信号通路进行了全面研究,靶向肺组织以及HFL细胞。
结果:在体外设置的范围内,结核菌素表现出1.9mM的IC50。此外,羟脯氨酸的分泌水平显着降低了50%以上,纤连蛋白,胶原蛋白I型,胶原蛋白III型和α-SMA。在体内,在50%以上的动物模型中,结核菌素能显著改善呼吸功能,降低羟脯氨酸,肺部炎症和胶原沉积。在内部和外部细胞环境中都发现了TGF-β/smad途径功能的显着下降。
结论:Tuberostemonine被认为是减轻纤维化的调节剂,可能成为肺纤维化的新方法。
OBJECTIVE: Tuberostemonine has several biological activity, the aim of study examined the impact of tuberostemonine on the proliferation of TGF-β1 induced cell model, and its ability to alleviate pulmonary fibrosis stimulated by
bleomycin in mice.
METHODS: In vitro, we assessed the effect of tuberostemonine (350, 550 and 750 µM) on the proliferation of cells stimulated by TGF-β1 (10 μg/L), as well as on parameters such as α-SMA vitality, human fibronectin, collagen, and hydroxyproline levels in cells. In vivo, we analyzed inflammation, hydroxyproline, collagen activity and metabolomics in the lungs of mice. Additionally, a comprehensive investigation into the TGF-β/smad signaling pathway was undertaken, targeting lung tissue as well as HFL cells.
RESULTS: Within the confines of an in vitro setup, the tuberostemonine manifested a discerned IC50 of 1.9 mM. Furthermore, a significant reduction of over fifty percent was ascertained in the secretion levels of hydroxyproline, fibronectin, collagen type I, collagen type III and α-SMA. In vivo, tuberostemonine obviously improved the respiratory function percentage over 50% of animal model and decreased the hydroxyproline, lung inflammation and collagen deposition. A prominent decline in TGF-β/smad pathway functioning was identified within both the internal and external cellular contexts.
CONCLUSIONS: Tuberostemonine is considered as a modulator to alleviate fibrosis and may become a new renovation for pulmonary fibrosis.