Objective To observe the effects of 7,8-dihydroxyflavone (7,8-DHF) on hypoxia induced endoplasmic reticulum stress (ERS) in human proximal tubular epithelial cells (HK-2).Methods The mRNA level of ERS associated biomarkers was evaluated by RT-PCR assay in cell hypoxia damaged model.And HK-2 cells were pretreated with different concentrations of 7,8-DHF through CCK-8 assay;meanwhile CCAAT/enhancer-binding protein homologous protein (CHOP),Cyr61,Akt and p-Akt were determined by western blotting assay.Moreover,HK-2 cells were pretreated by LY294002,a kind of PI3K/Akt inhibitor,to inhibit the PI3K/Akt signaling,and its effects on protein level induced by 7,8-DHF was detected.HK-2 cells was then over-expressed Cyr61 and exposed to hypoxia Apoptosis rate and CHOP expression were determined.Results Compared to hypoxia group (P ＜ 0.01),Hypoxia for 12h was effective in inducing ERS (P ＜ 0.01),while pretreatment with 7,8-DHF (100 μmol/L) increased cell proliferation significantly.The protein expressions of Cyr61 and p-Akt in H+7,8-DHF group were higher,but the level of CHOP was decreased (P ＜ 0.05).With LY294002 pretreated,the expression of Cyr61,p-Akt was down-regulated (all P ＜ 0.05) while the expression of CHOP was up-regulated (P ＜ 0.05).In comparison to empty plasmid group,when cells were transfected with over-expression of Cyr61 plasmid and exposed to hypoxia,the number of apoptotic tubular cells was decreased (P ＜ 0.01).And over-expression of Cyr61 significantly reducedCHOP expression compared with the empty plasmid group (P ＜ 0.01).Conclusion Pretreatment of 7,8-DHF could protect cells from hypoxia injury and inhibit ERS,which may involve the Akt-Cyr61 signaling pathway.