探讨薯蓣皂苷（dioscin）对尿酸（uric acid，UA）诱导的人肾小管上皮细胞（HK-2）氧化应激损伤的 影响及分子机制。方法将HK-2 细胞分为正常组、模型组（尿酸刺激造模）、条件对照组（尿酸+DMSO）和薯 蓣皂苷组（尿酸+薯蓣皂苷）。通过尿酸诱导HK-2 细胞氧化应激损伤模型；采用CCK-8 法检测细胞活力，流式 细胞技术检测细胞活性氧（ROS）水平，Real-time PCR 法检测糖原合成激酶3（GSK3β）、核转录因子红系2 相 关因子2（Nrf2）和血红素加氧酶1（HO-1）在mRNA 水平的表达，Western Blot 法检测GSK3β、磷酸化糖原合成 激酶3（p-GSK3β）、Nrf2 及HO-1 在蛋白水平的表达。结果经尿酸刺激后，HK-2 细胞的活力明显下降， ROS 水平明显升高（均P＜0.001）。经薯蓣皂苷治疗后，HK-2 细胞的活力增加，ROS 水平明显降低（均P＜ 0.001）。在蛋白及mRNA 水平上，尿酸刺激后Nrf2 和HO-1 的表达均下降，薯蓣皂苷干预后Nrf2 和HO-1 表 达均明显增加（均P＜0.001）。在蛋白水平上，模型组细胞p-GSK3β/GSK3β 比值较正常组明显下降，经薯蓣皂 苷干预后p-GSK3β/GSK3β 比值升高（均P＜0.001）。结论薯蓣皂苷可能是通过促进GSK3β 的磷酸化，激活 Nrf2/HO-1 通路，从而缓解尿酸诱导的HK-2 细胞氧化应激损伤。

To investigate the effect of dioscin on uric acid（UA）-induced oxidative stress injury of human renal tubular epithelial cells（HK-2）and its molecular mechanism. Methods HK-2 cells were cultured and divided into four groups： blank group （normal group）， model group （uric acid-stimulation modeling）， condition control group （UA+DMSO） and dioscin group （UA+dioscin） . Oxidative stress injury model was induced by UA in HK-2 cells. Cells viability was detected by CCK-8. ROS level was detected by flow cytometry. Real-time PCR was used to detect the expressions of glycogen synthase kinase 3β（GSK3β），nuclear factor erythroid 2- related factor 2（Nrf2） and heme oxygenase 1（HO-1） at mRNA level， and Western Blot was used to detect the expressions of phosphorylated glycogen synthesis kinase 3β（p-GSK3β），GSK3β，Nrf2 and HO-1 at protein level. Results After stimulation by UA，HK-2 cells viability was obviously decreased，and ROS level was significantly increased（all P＜ 0.001） . When treated with dioscin， HK-2 cells viability was obviously increased， and the ROS level of HK-2 cells was significantly decreased （all P＜0.001） . The expressions of Nrf2 and HO-1 decreased at the protein and mRNA levels after stimulation with UA. But the expressions of Nrf2 and HO-1 significantly increased after treated with dioscin （all P＜0.001） . Compared with the blank group， the p-GSK3β/GSK3β ratio in the model group decreased significantly at the protein level，but the p-GSK3β/GSK3β ratio increased after treated with dioscin （all P＜0.001） . Conclusion Dioscin can alleviate UA-induced oxidative stress injury in HK-2 cells. The mechanism might be that dioscin can promote phosphorylation of GSK3β，and activate Nrf2/HO-1 pathway.

R285.5

国家自然科学基金项目（81973765）。