The Significance Of SIRT1 Abnormal Expression In Placentas Of Intrahepatic Cholestasis Of Pregnancy

Objective To detect the protein expression of NF-!B and SIRT1 in normal and ICP placenta tissues. Investigate the inflammation reaction of HTR-8 cell line induced by taurocholic acid(TCA), the effect and mechanism of resveratrol in inhibiting the inflammation reaction.Methods Liver function index and placenta tissues of control and ICP patients were collected, and then the localization and protein quantitative expression of SIRT1 and NF-!B were detected. Different concentrations of TCA(Group1:TCA=0 #mol/L, Group2:TCA=2 #mol/L, Group3:TCA=20 #mol/L, Group4:TCA=100 #mol/L)were used to treat the HTR-8 cells for 24 hours, immunofluorescence and western blotting were used to detect the localization of SIRT1 and protein quantitative expression of SIRT1,NF-!B and TNF-α. Resveratrol,an agonist of SIRT1,accompanied with or without EX-527,an inhibitor of SIRT1, were used to treat all groups of HTR-8 cells for 24 hours, and then the protein quantitative expression of SIRT1,NF-!B and TNF-αwere detected by western blotting.Results Both SIRT1 and NF-!B were located in cytoplasm and nucleus of syncytiotrophoblasts. The expression of SIRT1 was significantly higher in control placental tissues than ICP placental tissues,the expression of NF-!B and TNF-αwere on the contrary(p<0.05). The expression of SIRT1 was significantly higher in group 1 and group 2 than group 3 and group 4,the expression of NF-!B and TNF-αwere on the contrary(p<0.05), the protein expression of SIRT1 turned to be higher,and the protein expression of NF-!B and TNF-αturned to be lower both in group 3 and group 4 after treated with resveratrol(p<0.05). The expression of SIRT1 was lower,the expression of NF-!B and TNF-αwere higher both in group 3 and group 4 after treated with resveratrol and EX-527 at the same time compared with treated by resveratrol alone(p<0.05).Conclusion Protein expression of SIRT1 decreased and NF-!B elevated in syncytiotrophoblasts of ICP compared with normal,the potential mechanism is SIRT1-NF-!B pathway were disrupted by high level of bile acids,and resveratrol can reverse the process.