Abstract： Objective： To investigate whether Triptolide （TP） restores autophagy in HK-2 cells under high- glucose conditions by regulating the Aldolase A/AMP-activated protein kinase/mammalian target of rapamycin （ALDOA/ AMPK/mTOR） signaling pathway. Methods：A high-glucose injury model was established using the standard cultured human renal tubular epithelial cell line HK-2. The cells were divided into the following groups ： control group （5.5 mmol/L glucose），high-glucose group （High G： 25 mmol/L glucose），low-dose TP group （TP-L： 25 mmol/L glucose + 10 nmol/L TP），high-dose TP group（ TP-H：25 mmol/L glucose + 20 nmol/L TP），siALDOA group（ 25 mmol/L glucose + 50 nmol/L siALDOA），and siALDOA+TP-L 组 （25 mmol/L glucose + 50 nmol/L siALDOA+10 nmol/L TP）. All groups were treated for 48 hours. Changes in cell proliferation viability were detected by MTT colorimetric assay； apoptosis rate was quantitatively analyzed by PI staining combined with flow cytometry；changes in autophagic flux were detected by the MDC method； subcellular localization and expression levels of the autophagy marker LC3-Ⅱ protein were detected by immunofluorescence；and changes in the protein expression of the key glycolytic enzyme ALDOA were detected by Western Blot. To further verify the mechanism，ALDOA expression was knocked down in HK-2 cells of the high-glucose model group using siRNA transfection technology. Combined with low-dose TP intervention， protein expression of ALDOA， p-AMPK， and p-mTOR was detected by Western Blot， and gene expression of ALDOA， AMPK，and mTOR was detected by RT-qPCR. Results：Cell function experiments showed that the proliferation rate of HK-2 cells in the HG group significantly decreased to （30.69 ± 5.96）%；whereas after TP intervention，it recovered in a dose-dependent recovery，reaching（ 50.11 ± 7.97）% in the TP-L group and（ 62.78 ± 11.64）% in the TP-H group， with statistically significant differences compared to the HG group （P＜0.05）. Apoptosis detection revealed that the apoptosis rate in the HG group increased to （49.34 ± 2.52）%；whereas it decreased to （23.89 ± 0.76）% in the TP-L group and （13.48 ± 2.33）% in the TP-H group，showing statistically significant differences compared to the HG group （P＜0.05）. Compared with the HG group， autophagic flux and LC3- Ⅱ expression were significantly increased （P＜0.05），and ALDOA expression was significantly decreased （P＜0.05） in the TP-L group. Mechanistic studies showed that compared with the HG group，mTOR pathway activation was significantly reduced in both the siALDOA group and the TP-L group （P＜0.05），while AMPK phosphorylation levels were significantly enhanced （P＜ 0.05）. Notably，there were no statistically significant differences in the indicators between the siALDOA+TP-L group and the siALDOA group （P＞0.05）. Conclusion： TP can effectively restore autophagy in HK-2 cells under highglucose conditions，and its mechanism is related to the inhibition of the ALDOA/AMPK/mTOR signaling pathway activation.