Abstract：Objective To clarify the effect of astragalus polysaccharide （AP） on insulin resistance model of HepG2 cells induced by hyperinsulinemia and its underlying molecular mechanism in lipid metabolism and oxidative stress. Methods HepG2 cells were divided into three groups： the control group was treated without any intervention; the model group was treated with 200 μL cell culture medium containing 10-6 mol/L insulin for 48 hours to build an insulin resistance model; the AP group was treated with optimal concentration of AP based on an insulin resistance model. After 24 hours, the concentration of H2O2 and the expression of PPARγ in each group were detected. Results AP could improve the survival rate of insulin-resistant HepG2 cells in a dose-dependent manner. The highest survival rate of the cells was （118.26±1.17）% with 10 μM AP. The concentration of H2O2 in the AP group was （0.82±0.09） μM, which was lower than （1.30±0.16） μM in the model group （P<0.05）, but was close to （0.78±0.09） μM in the control group （P>0.05）. The relative mRNA expression of PPARγ in the AP group was 0.96±0.04, which was higher than 0.51±0.05 in the model group （P<0.05）, but was close to 1.00±0.11 in the control group （P>0.05）. Conclusions In the insulin resistance model in vitro, AP can significantly increase the cell survival rate, reduce intracellular H2O2 concentration, and promote the expression of PPARγ. The mechanism may be related to lipid metabolism.
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