hirsutin通过Keap1/Nrf2通路减弱糖尿病肾病的氧化应激和自噬

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2025-04-07 DOI:10.1016/j.jphs.2025.04.002

Yao Zhang , Bing Yang , Miao Tan, Jinchuan Tan

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引用次数: 0

摘要

目的探讨多毛素对糖尿病肾病（DKD）的治疗潜力及肾保护机制。方法采用高脂饲料（HFD）和链脲佐菌素（STZ）诱导sd大鼠DKD模型。高糖（HG）刺激的HK-2细胞作为体外模型。采用双氢乙啶（DHE）染色法测定肾组织中的活性氧（ROS）水平。ELISA法测定大鼠组织和HK-2细胞中MDA、SOD和GSH的含量。Western blot和免疫荧光分析评估肾纤维化、Nrf2信号通路和自噬相关蛋白（Beclin 1, LC3I/II, P62）。结果舒坦治疗可显著改善大鼠的代谢和肾脏参数，增强肾功能，减少纤维化，表现为降低Vimentin、Collagen-IV和α-SMA的水平。通过降低ROS和MDA水平，提高SOD和GSH活性来缓解氧化应激。此外，hirsutin增强了自噬，表现为Beclin 1和LC3I/II水平升高，P62表达降低。通过破坏Keap1-Nrf2相互作用，毛素增加了Nrf2水平，上调了NQO1、SOD-2和HO-1等抗氧化酶。结论毛茸素通过调节Keap1/Nrf2通路，减轻氧化应激，促进自噬，对DKD具有肾保护作用，是治疗DKD的理想药物。

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Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway

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Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway

Objectives

To investigate the therapeutic potential and renal protective mechanisms of hirsutine in diabetic kidney disease (DKD).

Methods

A DKD model was induced in Sprague-Dawley rats using a high-fat diet (HFD) and streptozotocin (STZ). High glucose (HG)-stimulated HK-2 cells served as an in vitro model. Reactive oxygen species (ROS) levels in kidney tissues were measured using dihydroethidium (DHE) staining. ELISA was performed to measure MDA, SOD, and GSH in both rat tissues and HK-2 cells. Western blot and immunofluorescence analyses evaluated renal fibrosis, the Nrf2 signaling pathway, and autophagy-related proteins (Beclin 1, LC3I/II, P62).

Results

Hirsutine treatment significantly improved metabolic and renal parameters in rats, enhancing renal function and reducing fibrosis, as shown by lower levels of Vimentin, Collagen-IV, and α-SMA. It alleviated oxidative stress, indicated by reduced ROS and MDA levels and increased SOD and GSH activity. Additionally, hirsutine enhanced autophagy, reflected by higher Beclin 1 and LC3I/II levels and decreased P62 expression. By disrupting the Keap1-Nrf2 interaction, hirsutine increased Nrf2 levels and upregulated antioxidative enzymes like NQO1, SOD-2, and HO-1.

Conclusion

Hirsutine exhibited renoprotective effects in DKD by modulating the Keap1/Nrf2 pathway, mitigating oxidative stress and promoting autophagy, making it a promising candidate for treatment.

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.