Wang Nan, Feng Hui, Zhang Ziwei, Tian Haolin, Gu Ling, Bian Yong, Xue Mei
School of Integrative Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, 210023, China.
School of Chinese Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, 210023, China.
J Ethnopharmacol. 2025 Feb 11;341:119357. doi: 10.1016/j.jep.2025.119357. Epub 2025 Jan 10.
Danggui Buxue Decoction (DBD) is a classic traditional Chinese herbal formulation, composed of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) in a ratio of 5:1. It is a traditional Chinese medicine classic prescription for nourishing Qi and Yin (vital energy and body fluids), and it is effective in treating various clinical diseases. Diabetic nephropathy (DN) is categorized under "thirsting," "edema," and "turbid urine" in Traditional Chinese Medicine (TCM). However, the underlying mechanisms by which DBD ameliorates diabetic nephropathy remain unclear.
To explore the mechanism by which Danggui Buxue Decoction (DBD) regulates podocyte autophagy in diabetic nephropathy (DN).
Male db/m mice served as controls; db/db mice were divided into the model, dapagliflozin, and high/low-dose DBD groups. After 12 weeks of gavage, body weight, fasting blood glucose, urine albumin-to-creatinine ratio, 24-h urine volume, and blood urea nitrogen were recorded. Renal autophagy was assessed by Masson staining; mRNA levels were measured by qRT-PCR; and protein expression was analyzed by Western blot. The expression of inflammatory factors in the kidney was measured by ELISA. Human renal podocytes were cultured in NG, HG, HG + Blank serum, and HG + DBD-containing serum groups for 48 h; cell viability was measured by CCK-8, and autophagy was observed by transmission electron microscopy. Changes in autophagy protein and mRNA expression were observed after miR-27a transfection under high glucose conditions.
DBD can ameliorate renal function and reduce the degree of renal fibrosis in DN mice, enhance the mRNA expression of Beclin-1 and ULK1, and decrease the mRNA expression of Vimentin and α-SMA. This trend mirrors protein expression, and DBD also lowers renal inflammatory factors. DBD-containing serum boosts human renal podocyte viability under high glucose, protecting cells and modulating mRNA levels of Beclin-1, ULK1, P62, and PI3K, with miR-27a-mimic reversing these effects. DBD-containing serum also enhances Beclin-1, suppresses P62, and reduces the expression of p-PI3K/PI3K and p-AKT/AKT.
DBD Regulates Autophagy to Improve Renal Fibrosis in Diabetes via the miR-27a/PI3K/AKT Pathway.
当归补血汤（DBD）是一种经典的传统中药配方，由黄芪（AR）和当归（ASR）按5:1的比例组成。它是一种用于益气养阴（元气和体液）的传统中药经典方剂，对治疗多种临床疾病有效。糖尿病肾病（DN）在传统中医（TCM）中归类于“消渴”“水肿”和“尿浊”范畴。然而，当归补血汤改善糖尿病肾病的潜在机制仍不清楚。
探讨当归补血汤（DBD）调节糖尿病肾病（DN）中足细胞自噬的机制。
雄性db/m小鼠作为对照；db/db小鼠分为模型组、达格列净组和高/低剂量DBD组。灌胃12周后，记录体重、空腹血糖、尿白蛋白与肌酐比值、24小时尿量和血尿素氮。通过Masson染色评估肾脏自噬；通过qRT-PCR测量mRNA水平；通过蛋白质免疫印迹法分析蛋白质表达。通过ELISA测量肾脏中炎症因子的表达。人肾足细胞在正常葡萄糖（NG）、高葡萄糖（HG）、HG + 空白血清和HG + 含DBD血清组中培养48小时；通过CCK-8测量细胞活力，通过透射电子显微镜观察自噬。在高糖条件下进行miR-27a转染后，观察自噬蛋白和mRNA表达的变化。
当归补血汤可改善糖尿病肾病小鼠的肾功能，降低肾脏纤维化程度，增强Beclin-1和ULK1的mRNA表达，降低波形蛋白和α-SMA的mRNA表达。这种趋势与蛋白质表达一致，且当归补血汤还可降低肾脏炎症因子水平。含当归补血汤的血清在高糖条件下可提高人肾足细胞活力，保护细胞并调节Beclin-1、ULK1、P62和PI3K的mRNA水平，而miR-27a模拟物可逆转这些作用。含当归补血汤的血清还可增强Beclin-1表达，抑制P62表达，并降低p-PI3K/PI3K和p-AKT/AKT的表达。
当归补血汤通过miR-27a/PI3K/AKT途径调节自噬以改善糖尿病中的肾纤维化。
