Ke Jingjing, Zang Hualong, Liu Yang, Teng Qiuping, Hua Jiao, Peng Dan, Wang Ping
Department of Nephrology, Jingmen Central Hospital, Hubei Minzu University, Jingmen, Hubei, China.
Department of Nephrology, Jingmen Central Hospital Affiliated to Jingchu University of Technology, Jingmen, Hubei, China.
Front Pharmacol. 2024 Nov 15;15:1480629. doi: 10.3389/fphar.2024.1480629. eCollection 2024.
This study aims to explore the role and investigate mechanisms of β-Cryptoxanthin (BCX) in high glucose (HG)-induced podocyte injury and renal dysfunction.
In this study, db/db mice were orally treated with BCX. Blood glucose, body weight, urinary albumin creatinine ratio (ACR) were recorded to evaluate the mice renal function. The H&E, PAS staining, and transmission electron microscopy (TEM) were utilized to examine the effect of BCX on the morphological changes of glomeruli in db/db mice. In addition, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP) level, ATP level, and SA-β-gal staining were used to assess the podocyte oxidative damage, mitochondrial dysfunction and senescence. Furthermore, the effects of BCX on Nrf2/HO-1 signaling pathway were evaluated and through Western blotting, immunohistochemistry and immunofluorescence analysis.
, BCX reversed glomerular mesangial matrix expansion and reduced proteinuria in db/db mice, as well as decreased glomerular oxidative stress and kidney aging. Similarly, study showed that BCX effectively alleviated the oxidative stress, mitochondrial dysfunction, and senescence induced by HG in podocytes. Furthermore, we identified that the antioxidative effects of BCX are associated with the activation of Nrf2/HO-1 signaling pathway, and that Nrf2 knockdown partially abrogated the protective effects of BCX .
Our study demonstrated for the first time that BCX alleviates podocyte injury in DKD by promoting Nrf2/HO-1 signaling pathways. BCX may be a potential candidate compound for preventing Diabetic kidney disease (DKD).
本研究旨在探讨β-隐黄质（BCX）在高糖（HG）诱导的足细胞损伤和肾功能障碍中的作用并研究其机制。
在本研究中，对db/db小鼠进行BCX口服治疗。记录血糖、体重、尿白蛋白肌酐比值（ACR）以评估小鼠肾功能。采用苏木精-伊红（H&E）染色、过碘酸雪夫（PAS）染色和透射电子显微镜（TEM）检查BCX对db/db小鼠肾小球形态变化的影响。此外，利用活性氧（ROS）含量、线粒体膜电位（MMP）水平、三磷酸腺苷（ATP）水平和衰老相关β-半乳糖苷酶（SA-β-gal）染色评估足细胞氧化损伤、线粒体功能障碍和衰老情况。此外，通过蛋白质免疫印迹法、免疫组织化学和免疫荧光分析评估BCX对核因子E2相关因子2/血红素加氧酶-1（Nrf2/HO-1）信号通路的影响。
BCX可逆转db/db小鼠肾小球系膜基质扩张并减少蛋白尿，同时降低肾小球氧化应激和肾脏衰老。同样，研究表明BCX可有效减轻HG诱导的足细胞氧化应激、线粒体功能障碍和衰老。此外，我们发现BCX的抗氧化作用与Nrf2/HO-1信号通路的激活有关，并且Nrf2基因敲低部分消除了BCX的保护作用。
我们的研究首次证明BCX通过促进Nrf2/HO-1信号通路减轻糖尿病肾病（DKD）中的足细胞损伤。BCX可能是预防糖尿病肾病（DKD）的潜在候选化合物。
