毛蕊异黄酮通过靶向Notch1/Snail信号通路改善肾病综合征中的蛋白尿。
Calycosin ameliorates albuminuria in nephrotic syndrome by targeting Notch1/Snail pathway.
作者信息
Ma Xiaohong, Guan Binghe, Pang Linrong
机构信息
Department of Nephrology, Shenzhen Bao'an Authentic TCM Therapy Hospital, Room 1703, Block G, Jiazhou Business Center, Baomin 1 Road, Xin 'an Street, Bao 'an District, Shenzhen, Guangdong, 518100, China.
Department of Internal Medicine, Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen, 518100, China.
出版信息
BMC Nephrol. 2025 Apr 18;26(1):198. doi: 10.1186/s12882-025-04113-3.
BACKGROUND
Heavy proteinuria is an important hallmark for kidney disease including nephrotic syndrome. Astragali Radix, a traditional Chinese herb, holds the potential to alleviate nephrotic syndrome; however, the underlying mechanism has not been completely clarified. The study aimed to explore the role of calycosin (CHO), a major active component of Astragali Radix, in regulating adriamycin-induced proteinuria.
METHODS
A rat model of nephrotic syndrome was established through two adriamycin injections within two weeks (4 mg/kg for the first week and 2 mg/kg for the second week). After the induction of renal injury, 10 mg/kg or 20 mg/kg calycosin was intraperitoneally injected into rats for four weeks. Before euthanasia of rats, urine and blood samples were collected, and body weight was recorded. Then, 24 h urine protein content, kidney index, total cholesterol (TC), triglyceride (TG), as well as renal function indicators including blood urea nitrogen (BUN), serum creatinine (SCR), and urine albumin excretory rate (UAE) were measured. Hematoxylin-eosin staining for renal cortex tissues was performed to evaluate glomerular structural damage. TUNEL assay was performed to evaluate renal cell apoptosis. Western blotting was conducted to measure protein levels of podocyte-specific markers (podocin and nephrin), Notch1, and Snail in rat renal tissues.
RESULTS
Calycosin reversed adriamycin-induced increase in proteinuria content, kidney index, and concentrations of renal function indicators. Calycosin ameliorated glomerular structural damage, inflammatory cell infiltration, and basement membrane thickening in model rats. In addition, calycosin rescued the suppressive impact of adriamycin on renal cell apoptosis and protein levels of podocyte markers. The activated Notch1/Snail signaling in model rats was suppressed by calycosin intervention.
CONCLUSION
Calycosin exerts a protective role against adriamycin-induced nephrotic syndrome via inhibition of the Notch1/Snail signaling.
CLINICAL TRIAL DETAILS
Not applicable.
背景
大量蛋白尿是包括肾病综合征在内的肾脏疾病的重要标志。黄芪，一种传统中药，具有缓解肾病综合征的潜力；然而，其潜在机制尚未完全阐明。本研究旨在探讨黄芪的主要活性成分毛蕊异黄酮（CHO）在调节阿霉素诱导的蛋白尿中的作用。
方法
通过在两周内两次注射阿霉素（第一周4mg/kg，第二周2mg/kg）建立肾病综合征大鼠模型。肾损伤诱导后，将10mg/kg或20mg/kg毛蕊异黄酮腹腔注射到大鼠体内，持续四周。在大鼠安乐死之前，收集尿液和血液样本，并记录体重。然后，测量24小时尿蛋白含量、肾脏指数、总胆固醇（TC）、甘油三酯（TG）以及包括血尿素氮（BUN）、血清肌酐（SCR）和尿白蛋白排泄率（UAE）在内的肾功能指标。对肾皮质组织进行苏木精-伊红染色以评估肾小球结构损伤。进行TUNEL检测以评估肾细胞凋亡。进行蛋白质印迹法以测量大鼠肾组织中足细胞特异性标志物（足突蛋白和nephrin）、Notch1和Snail的蛋白水平。
结果
毛蕊异黄酮逆转了阿霉素诱导的蛋白尿含量、肾脏指数和肾功能指标浓度的增加。毛蕊异黄酮改善了模型大鼠的肾小球结构损伤、炎性细胞浸润和基底膜增厚。此外，毛蕊异黄酮挽救了阿霉素对肾细胞凋亡和足细胞标志物蛋白水平的抑制作用。毛蕊异黄酮干预抑制了模型大鼠中激活的Notch1/Snail信号通路。
结论
毛蕊异黄酮通过抑制Notch1/Snail信号通路对阿霉素诱导的肾病综合征发挥保护作用。
临床试验详情
不适用。
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