Jian-Pi-Gu-Shen-Hua-Yu Decoction Alleviated Diabetic Nephropathy in Mice through Reducing Ferroptosis

IF 3.6 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Research Pub Date : 2024-03-16 DOI:10.1155/2024/9990304

Shuquan Lv, Lirong Fan, Xiaoting Chen, Xiuhai Su, Li Dong, Qinghai Wang, Yuansong Wang, Hui Zhang, Huantian Cui, Shufang Zhang, Lixin Wang

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引用次数: 0

Abstract

Background. Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. Purpose. The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. Materials and Methods. We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. Results. The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. Conclusion. JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.

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健脾益肾汤通过减少铁蛋白沉积缓解小鼠糖尿病肾病

背景。糖尿病肾病（DN）是糖尿病最常见的并发症之一，也是终末期肾病的主要病因。然而，目前的治疗方法仍无法有效阻止 DN 的进展。健脾益肾汤可用于治疗 DN 等慢性肾病，但其具体作用机制尚未完全阐明。研究目的本研究的目的是阐明太子参汤是否能通过抑制高铁血症来缓解糖尿病肾病的进展。材料与方法。我们建立了 DN 小鼠模型，以研究 JPGS 在 DN 小鼠模型中的治疗效果。随后，我们研究了 JPGS 对铁蛋白沉积和谷胱甘肽过氧化物酶 4（GPX4）通路相关指标的影响。最后，我们使用 GPX4 抑制剂和铁突变抑制剂验证了 JPGS 是否通过 GPX4 通路抑制了 DN 小鼠的铁突变。结果显示结果表明，JPGS 对 DN 小鼠有治疗作用，能改善肾功能并减轻炎症反应。此外，JPGS 治疗降低了铁超载和氧化应激水平，同时上调了 GPX4 通路相关蛋白的表达。此外，在治疗 DN 的过程中，JPGS 表现出了与 Fer-1 类似的治疗效果，而 RSL3 能够抵消 JPGS 的治疗效果和抗增殖作用。结论JPGS对DN小鼠具有明显的治疗和抗炎作用，其机制主要是通过上调GPX4通路相关蛋白的表达，从而缓解铁超载，最终减轻铁变态反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Diabetes Research ENDOCRINOLOGY & METABOLISM-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

8.40

自引率

2.30%

发文量

152

审稿时长

14 weeks

期刊介绍： Journal of Diabetes Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications, such as diabetic retinopathy, neuropathy and nephropathy.