Abstract:

Objective To discuss the expression changes of poly（rC）-binding protein 1 （PCBP1）， ferritin heavy chain 1 （FTH1）， and glutathione peroxidase 4 （GPX4） proteins in placental tissue from the postpartum women with preeclampsia （PE） and the human trophoblast cells HTR-8/SVneo after treated with hypoxia or erastin， and to clarify their mechanisms. Methods The placental tissues were collected from 12 postpartum women with PE （PE group） and 12 women with normal pregnancy （normal group）. Transmission electron microscope was used to observe the ultrastructures of placental trophoblasts； immunohistochemistry and Western blotting methods were used to detect the expression levels of PCBP1 and GPX4 proteins in placental tissue of the women in two groups. The HTR-8/SVneo cells were treated with different concentrations （0， 5， 10， 20， 40和80 μmol·L^-1） of erastin， and cell counting kit-8 （CCK-8） method was used to measure the cell viabilities to screen the erastin concentration. The HTR-8/SVneo cells were exposed to normal enulorment（normoxia group）， hypoxia （<1% O?， 24 h， hypoxia group） or erastin （0， 20， 40 μmol·L^-1）， and Western blotting method was used to detect the expression levels of PCBP1， FTH1 and GPX4 proteins in the cells under different treatments； Pearson correlation analysis was used to analyze the correlations between the expression level of PCBP1 protein in placental tissue of the postparum with PE and systolic and diastolic blood pressures. Results Compared with normal group， the placental trophoblasts in PE group showed obvious mitochondrial ultrastructural damage； the expression level of PCBP1 protein in placental tissue of the postpartum women PE group was increased （P<0.01）， while the expression level of GPX4 protein was decreased （P<0.01）. Compared with normoxia group， the expression levels of PCBP1 and FTH1 proteins in the HTR-8/SVneo cells in hypoxia group were increased （P<0.05 or P<0.01）， and the expression level of GPX4 protein was decreased （P<0.05）. Compared with 0 μmol·L^-1 erastin group， the cell viabilities in 20 and 40 μmol·L^-1 erastin groups were decreased （P<0.05）， the expression level of PCBP1， protein in the cells in 40 μmol·L^-1 erastin group and the expression levels of FTH1 proteins in the cells were increased （P<0.05）， and the expression levels of GPX4 protein in the cells in 20 and 40 μmol·L^-1 erastin groups were decreased （P<0.01）， but the difference in GPX4 protein expression level between 20 μmol·L^-1 erastin group and 40 μmol·L^-1 erastin group was not statistically significant （P>0.05）. The Pearson correlation analysis results showed that the expression level of PCBP1 protein in placental tissue of the postparum women was positively correlated with both systolic and diastolic blood pressure （r=0.761 4， P<0.01； P=0.623 9， P<0.01）. Conclusion The PCBP1 protein expression is increased and the GPX4 protein expression is decreased in placental tissue of the postpartum woment with PE； hypoxia and erastin treatment can increase the expressions of PCBP1 and FTH1 protein and decrease the expression of GPX4 protein in the HTR-8/SVneo cells， and their mechanisms may be related to iron homeostasis imbalance and impaired antioxidant defense.

Key words: Preeclampsia, Poly（rC）-binding protein 1, Ferritin heavy chain 1, Glutathione Peroxidase 4, Ferroptosis