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基于改善 AhR/NOX4 通路介导的氧化应激损伤,探究铁皮石斛多糖对单侧输尿管梗阻手术诱导的肾纤维化的治疗机制。

Therapeutic mechanism exploration of polysaccharides from Dendrobium officinale on unilateral ureteral obstruction operation-induced renal fibrosis based on improving oxidative stress injury mediated by AhR/NOX4 pathway.

机构信息

Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Huai'an, Jiangsu 223003, PR China.

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223002, PR China.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 3):126920. doi: 10.1016/j.ijbiomac.2023.126920. Epub 2023 Sep 17.

Abstract

Dendrobium officinale polysaccharides (DOP) has been reported to possess remarkable effects on improving renal function, oxidative stress damage and fibrotic diseases. However, the role and mechanism of DOP in preventing and treating renal fibrosis remain unclear. The purpose of this paper was to explore the therapeutic effects and underlying mechanisms of DOP on renal fibrosis. Firstly, renal fibrosis model was induced by unilateral ureteral obstruction operation (UUO) in male BALB/c mice. Subsequently, the anti-renal fibrosis effect of DOP was evaluated. It turned out that DOP significantly attenuated UUO induced renal fibrosis. The beneficial effects of DOP on renal fibrosis were concretely manifested in the relief of clinical symptoms, improvement of renal function, reduction of extracellular matrix collagen aggregation, attenuation of structural damage and inflammation, and decrement of profibrotic factors secretion. Meanwhile, DOP could also alleviate oxidative stress injury and inhibit the AhR/NOX4 pathway proteins expression. Furthermore, multivariate statistical analysis, AhR interference and overexpression experiments showed that the effect of DOP on alleviating renal fibrosis was closely related to the improvement of oxidative stress injury mediated by the AhR/NOX4 pathway. Overall, the data in the present paper indicated that DOP could alleviate renal fibrosis through improving AhR/NOX4 mediated oxidative stress injury.

摘要

铁皮石斛多糖(DOP)已被报道具有改善肾功能、氧化应激损伤和纤维化疾病的显著作用。然而,DOP 预防和治疗肾纤维化的作用和机制尚不清楚。本文旨在探讨 DOP 对肾纤维化的治疗作用及其潜在机制。首先,通过单侧输尿管梗阻手术(UUO)在雄性 BALB/c 小鼠中诱导肾纤维化模型。随后,评估了 DOP 的抗肾纤维化作用。结果表明,DOP 显著减轻了 UUO 诱导的肾纤维化。DOP 对肾纤维化的有益作用具体表现在缓解临床症状、改善肾功能、减少细胞外基质胶原聚集、减轻结构损伤和炎症以及减少促纤维化因子的分泌。同时,DOP 还可以减轻氧化应激损伤并抑制 AhR/NOX4 通路蛋白的表达。此外,多元统计分析、AhR 干扰和过表达实验表明,DOP 减轻肾纤维化的作用与 AhR/NOX4 通路介导的氧化应激损伤改善密切相关。总体而言,本文数据表明,DOP 可以通过改善 AhR/NOX4 介导的氧化应激损伤来减轻肾纤维化。

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