桑孜古本多糖通过 Nrf2 介导的 TGF-β1/Smad7 信号通路调控,减缓糖尿病肾病中的肾上皮-间质转化

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Clinical Pharmacy and Therapeutics Pub Date : 2024-08-05 DOI:10.1155/2024/3475485
Jianing Zhang, Fan Wang, Chang Liu, Xiangyi Lu, Weiping Xu, Yang Yu, Shasha Bai, Zhilian Chen
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摘要

背景。桑日古本多糖(SZP)具有保护肾脏的特性,可以减轻糖尿病肾病(DM)患者的肾脏纤维化。然而,SZP 保护肾脏作用的机制尚不清楚。研究目的我们的研究旨在阐明 SZP 对 DM 肾脏保护作用的机制。材料与方法。本研究以链脲佐菌素诱导的 C57BL/6J 糖尿病肾病小鼠和高糖联合 TGF-β1 诱导的 HK-2 细胞 EMT 为研究对象。用 ShRNA 构建的 Nrf2 敲除 HK-2 细胞来探讨 Nrf2 在桑梓古本多糖抑制上皮-间质转化中的作用。结果显示结果表明,在体内,桑梓古本多糖可改善肾脏上皮-间质转化和氧化应激,SZP可激活肾脏Nrf2、增加Smad7和抑制TGF-β1的表达(分别为1.05-0.71倍、1.66-0.40倍和0.96-1.31倍)。在体外,SZP 可改善 HG 联合 TGF-β1 诱导的 HK-2 细胞上皮-间质转化,增加 Nrf2 和 Smad7 的表达,抑制 TGF-β1 的表达(分别为 1.50-1.12 倍、1.49-1.07 倍和 0.94-1.38 倍)。此外,桑孜古本多糖对 Nrf2 敲除的 HK-2 细胞的上述作用也有所减弱。结论研究结果表明,桑枝多糖可通过 Nrf2 介导的 TGF-β1/Smad7 信号通路调控改善糖尿病肾病的肾上皮-间充质转化。
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Sanziguben Polysaccharides Attenuate Renal Epithelial-Mesenchymal Transition in Diabetic Nephropathy through Nrf2-Mediated Regulation of TGF-β1/Smad7 Signaling Pathway

Context. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. Objectives. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. Materials and Methods. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-β1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. Results. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-β1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-β1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-β1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. Conclusions. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-β1/Smad7 signaling pathway.

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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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