脂毒性在糖尿病肾疾病中的作用:从生理机制到治疗前景
The Role of Lipotoxicity in Diabetic Nephropathy: From Physiologic Mechanisms to Therapeutic Perspectives
摘要: 脂质代谢稳态在维持细胞功能和能量代谢方面起着关键作用。在正常情况下,细胞通过脂质摄取、合成、消耗和输出维持代谢稳态。在糖尿病肾疾病(DKD)中,肾脏的脂质代谢稳态遭到严重破坏,导致脂质在肾小管上皮细胞和足细胞等肾实质细胞中异常积累。这种积累会引发包括氧化应激、线粒体功能障碍、自噬受损和炎症反应在内的病理变化。基于这些脂质积累和脂毒性机制的靶向治疗,如Nrf-2激动剂、PPAR-α激动剂和SGLT-2抑制剂等有望为未来DKD的治疗提供新方向。
Abstract: Lipid metabolic homeostasis plays a key role in maintaining cellular function and energy metabolism, and under normal conditions, cells maintain metabolic homeostasis through lipid uptake, synthesis, consumption and output. In diabetic kidney disease (DKD), lipid metabolic homeostasis in the kidney is severely disrupted, leading to abnormal lipid accumulation in renal parenchymal cells, such as tubular epithelial cells and podocytes. This accumulation triggers pathological changes, including oxidative stress, mitochondrial dysfunction, impaired autophagy, and inflammatory responses. Targeted therapies based on these mechanisms of lipid accumulation and lipotoxicity, such as Nrf-2 agonists, PPAR-α agonists, and SGLT-2 inhibitors, are expected to provide new directions for the treatment of DKD in the future.
文章引用:范家瑞, 印承孝, 杜晓刚. 脂毒性在糖尿病肾疾病中的作用:从生理机制到治疗前景[J]. 临床医学进展, 2025, 15(4): 2211-2224. https://doi.org/10.12677/acm.2025.1541172

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