Zhang Kejia, Li MiaoMiao, Yin Kaiwen, Wang Minjie, Dong Qiuchi, Miao Zilan, Guan Yubo, Wu Qi, Zhou Yao
Public Experimental Research Center, Xuzhou Medical University, Xuzhou, China.
Department of Pathophysiology, Xuzhou Medical University, Xuzhou, China.
Phytother Res. 2023 Dec;37(12):5871-5882. doi: 10.1002/ptr.7993. Epub 2023 Aug 30.
Renal tubular injury is a key factor in the progression of diabetic kidney disease to end-stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen-activated protein kinase signaling pathway, thereby alleviating proteinuria-induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment.
肾小管损伤是糖尿病肾病进展至终末期肾病的关键因素。金丝桃苷是多种植物中的一种天然黄酮醇苷，是临床治疗糖尿病肾病的一种潜在有效药物。然而，其具体机制尚不清楚。因此，本研究将探讨金丝桃苷对糖尿病肾病肾小管间质的作用及机制。db/db小鼠（C57BL/KsJ）是由瘦素受体点突变导致的2型糖尿病模型，会出现糖尿病肾病。因此，db/db小鼠用于体内实验研究。在体外，将人肾小管上皮细胞与牛血清白蛋白孵育，以模拟原尿中白蛋白过多引起的肾小管上皮细胞损伤。实验结果表明，金丝桃苷可改善小鼠肾功能，减轻肾组织损伤，并可抑制人肾小管上皮细胞的氧化应激、细胞外调节蛋白激酶1/2信号激活和细胞焦亡。因此，金丝桃苷通过调节细胞外调节蛋白激酶1/2/丝裂原活化蛋白激酶信号通路的激活来抑制氧化应激，从而减轻蛋白尿诱导的肾小管上皮细胞焦亡。本研究提供了新的证据，有助于金丝桃苷在糖尿病肾病治疗中的临床应用。
