Objective To investigate the effects of paeoniflorin on high-glucose-induced ferroptosis and the nuclear factor E2 related factor 2(NRF2)and heme oxygenase-1(HMOX-1)pathway in podocytes.Methods The mouse renal podocyte cell line MPC-5 was cultured in vitro.MPC-5 cells were induced with blank control,high-glucose,high-glucose + low-dose paeoniflorin,high-glucose + high-dose paeoniflorin,high-glucose + ML385 and high-glucose + ZNPP.Cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.Commercial kits were used to measure Fe2+,superoxide dismutase(SOD),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS)levels.The mRNA levels of Nrf2(NF-E2-related factor 2)and HMOX-1(heme oxygenase-1)were detected by Quantitative real-time polymerase chain reaction(QRT-PCR).Protein levels of Nrf2,HMOX-1,SLC7A11(olute carrier family 7 member 11)and GPX4(glutathione peroxidase 4)were detected by Western blot.Results Compared with those induced with blank control,MPC-5 cells induced with high-glucose presented significantly lower OD450 at 24h and 48h,SOD,GSH and protein levels of SLC7A11 and GPX4,and significantly higher Fe2+,MDA,ROS,apoptotic rate,mRNA and protein levels of Nrf2 and HMOX-1(P<0.05).Compared with those induced with high-glucose,MPC-5 cells induced with high-glucose + low-dose paeoniflorin,high-glucose + high-dose paeoniflorin,high-glucose + ML385 and high-glucose + ZNPP presented significantly higher OD450 at 24h and 48h,SOD,GSH and protein levels of SLC7A11 and GPX4,and significantly lower Fe2+,MDA,ROS,apoptotic rate,mRNA and protein levels of Nrf2 and HMOX-1(P<0.05).There were no significant differences in the above parameters between MPC-5 cells induced with high-glucose + high-dose paeoniflorin and high-glucose + ML385(P>0.05).Except for the significantly higher protein level of Nrf2(P<0.05),there were no significant differences in the remaining parameters between MPC-5 cells induced with high-glucose + high-dose paeoniflorin and high-glucose + ZNPP(P>0.05).Conclusion Paeoniflorin can inhibit ferroptosis of podocytes induced by high glucose by inhibiting the Nrf2/HMOX-1 pathway.
paeoniflorinhigh glucosepodocytenuclear factor E2 related factor 2(NRF2)and heme oxygenase-1(HMOX-1)(Nrf2/HMOX-1)pathway
NETL
NSTL
维普
万方数据
