Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, 100034, China.
Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, 100034, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118995. doi: 10.1016/j.jep.2024.118995. Epub 2024 Oct 26.
The underlying mechanisms of diabetic kidney disease (DKD) and effective treatment strategies remain unclear. DKD progression is closely associated with abnormal iron metabolism and ferroptosis in vivo. Leeches, used in traditional Chinese medicine for promoting blood circulation and resolving blood stasis, are utilized to treat diabetes and its associated complications. Leeches effectively antagonize oxidative stress injury and exert protective effects on renal function. However, whether leeches can inhibit ferroptosis by modulating oxidative stress and iron metabolism remains unclear.
To investigate the therapeutic potential of leech granules in DKD and, specifically, their effects on ferroptosis.
We used a mouse model of DKD. The mice were treated with leech granules via gavage. Component identification and analysis of leech granules were performed using UPLC-MS, and efficacy was assessed by histopathology and analysis of blood glucose, lipids, and renal function. Additionally, the pharmacological mechanisms of leech granules were explored via proteomics, immunohistochemical staining, western blotting, and cell culture.
Proteomic analysis showed that iron metabolism was dysregulated and ferroptosis increased in DKD mice. Leech granules significantly reduced iron accumulation and renal pathological damage, decreased ROS levels, upregulated GSH levels, and inhibited ferroptosis in the kidneys of DKD mice. Furthermore, in vitro cellular experiments demonstrated that leech granules could inhibit erastin-induced ferroptosis and protect renal cells.
The regulation of renal iron metabolism and inhibition of ferroptosis mediates the therapeutic effect of leech granules on DKD. Leech granules represent a promising approach for DKD treatment.
糖尿病肾病（DKD）的潜在机制和有效治疗策略仍不清楚。DKD 的进展与体内异常的铁代谢和铁死亡密切相关。在传统中医中，水蛭被用于促进血液循环和消除血瘀，用于治疗糖尿病及其相关并发症。水蛭能有效拮抗氧化应激损伤，对肾功能具有保护作用。然而，水蛭是否能通过调节氧化应激和铁代谢来抑制铁死亡尚不清楚。
探讨水蛭颗粒在 DKD 中的治疗潜力，特别是其对铁死亡的影响。
我们使用 DKD 小鼠模型。通过灌胃给予小鼠水蛭颗粒。采用 UPLC-MS 对水蛭颗粒进行成分鉴定和分析，并通过组织病理学和血糖、血脂、肾功能分析评估疗效。此外，通过蛋白质组学、免疫组化染色、Western blot 和细胞培养探讨了水蛭颗粒的药理学机制。
蛋白质组学分析表明，DKD 小鼠的铁代谢失调，铁死亡增加。水蛭颗粒显著减少了铁的积累和肾脏病理损伤，降低了 ROS 水平，增加了 GSH 水平，并抑制了 DKD 小鼠肾脏的铁死亡。此外，体外细胞实验表明，水蛭颗粒可抑制 erastin 诱导的铁死亡并保护肾细胞。
调节肾脏铁代谢和抑制铁死亡介导了水蛭颗粒对 DKD 的治疗作用。水蛭颗粒是治疗 DKD 的一种有前途的方法。
