Feng Jiashu, Zhang Weiliang, Liu Ruiqi, Xiang Ting, Wu Xinlin
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Zhongshan 2nd Road, Guangzhou, 510080, P. R. China.
Department of Traditional Chinese Medicine, The Second People's Hospital of Shuangliu District, Sixing Road, Chengdu, 610200, P. R. China.
BMC Nephrol. 2025 Jul 29;26(1):422. doi: 10.1186/s12882-025-04311-z.
This study aims to explore the therapeutic effects and mechanisms of dioscin on the UA-induced HK-2 cells fibrosis model by modulating oxidative stress and autophagy.
HK-2 cells fibrosis was constructed by UA stimulation. CCK8 was used to assess cell proliferation. Flow cytometry was employed to detect apoptosis. MDC staining was performed to observe the formation of autophagosomes. Western blot was used to evaluate the levels of oxidative stress, autophagy and fibrosis markers. The detection of ROS and Elisa assay were used to analyze the changes of oxidative stress.
Dioscin significantly inhibits cell apoptosis. Dioscin increases the expression of LC3, Beclin-1 and NRF2 and decreases the expression of P62 and KEAP1. Furthermore, dioscin inhibits the levels of ROS and MDA, and promotes the levels of SOD and CAT. Moreover, dioscin significantly downregulates the expression of TGF-β, FN, and Collagen I. However, the regulatory effects of dioscin on these indicators are inhibited when NRF2 is knocked down.
These results suggest that dioscin treats the UA-induced HK-2 cells fibrosis model by targeting the modulation of NRF2 to regulate oxidative stress and promote protective autophagy. The mechanism may be associated with the restoration of the P62-KEAP1-NRF2 signaling pathway.
Not applicable.
本研究旨在探讨薯蓣皂苷通过调节氧化应激和自噬对尿酸（UA）诱导的HK-2细胞纤维化模型的治疗作用及机制。
通过UA刺激构建HK-2细胞纤维化模型。采用CCK8法评估细胞增殖。运用流式细胞术检测细胞凋亡。进行MDC染色观察自噬体的形成。采用蛋白质免疫印迹法评估氧化应激、自噬和纤维化标志物的水平。通过检测活性氧（ROS）和酶联免疫吸附测定（ELISA）分析氧化应激的变化。
薯蓣皂苷显著抑制细胞凋亡。薯蓣皂苷增加微管相关蛋白1轻链3（LC3）、Beclin-1和核因子E2相关因子2（NRF2）的表达，降低P62和 Kelch样环氧氯丙烷相关蛋白1（KEAP1）的表达。此外，薯蓣皂苷抑制ROS和丙二醛（MDA）水平，提高超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平。而且，薯蓣皂苷显著下调转化生长因子-β（TGF-β）、纤连蛋白（FN）和I型胶原（Collagen I）的表达。然而，当NRF2被敲低时，薯蓣皂苷对这些指标的调节作用受到抑制。
这些结果表明，薯蓣皂苷通过靶向调节NRF2来治疗UA诱导的HK-2细胞纤维化模型，以调节氧化应激并促进保护性自噬。其机制可能与P62-KEAP1-NRF2信号通路的恢复有关。
不适用。
