Objective:To investigate the mechanism of H2S up-regulate SIRT1 to regulate the metabolism of cholesterol in the liver, thereby reducing the cholesterol level. Methods:HepG2 cells was used in the experiment. NaHS was exogenous H2S donor and LY294002 was the inhibitor of PI3K/AKT. HepG2 cells were cultivated with 4 different concentrations (0, 50, 100 and 200 μmol·L-1) of NaHS for 24 hours. Then the viability of HepG2 cells was detected by CCK-8 kits and the protein expressions of SIRT1were detected by western blot. Then 100 μmol·L-1 NaHS was selected to deal with HepG2 cells for 0 h, 6 h, 12 h, and 24 h respectively, western blot was used to detect SIRT1 protein expression. HepG2 cells were divided into blank control group, NaHS drug intervention group and LY294002+NaHS intervention group, then P-AKT, AKT and SIRT1 protein expressions were tested with western blot, gene expressions of SIRT1, SREBP-1c,SREBP-2,CYP7A1,HMGCR were detected with RT-qPCR. The cells were divided into blank control group, oleic acid intervention group (positive control),oleic acid+NaHS group and oleic acid+NaHS+LY294002 group, then intracellular cholesterol concentration were tested by using cholesterol testing kits. Results:Compared with the control group, 50,100,200 μmol·L-1 NaHS all had no effects on the viability of HepG2(P>0.05).The protein expressions of SIRT1 were increasing in a concentration and time dependence way and reached the maximum when the concentration was 100 μmol·L-1 and the time was 24 h(P<0.05). Compared with control group,H2S could increase P-AKT/AKT and SIRT1 protein expressions and CYP7A1 gene expression (P<0.05), inhibite SREBP-1c,SREBP-2 and HMGCR gene expressions (P<0.05), meanwhile, intracellular cholesterol levels reduced(P<0.05),using LY294002 processing cells in advance had the opposite effect. Conclusion:The PI3K/AKT/SIRT1 pathway is involved in the function of H2S in regulating cholesterol metabolism in the liver.
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