Mitochondrial Autophagy Protein And Fetal Doppler In Patients With Preeclampsia

Objective:To investigate the relationship between BNIP3 expression and disease development and its value with fetal umbilical artery flow parameters in assessing fetal status,we determined the expression levels of mitochondrial autophagy protein BCL2 adenovirus E1B19 k Da interaction protein 3(BNIP3)in serum and placenta of normal pregnant women and patients with preeclampsia(PE)and measured the associated hemodynamic indices of fetal Doppler umbilical artery(UA).Methods:According to the inclusion criteria,24 normal pregnant women and 24 preeclampsia pregnant women without complications were selected from the pregnant women who underwent cesarean section in the Department of Obstetrics of the second Norman bethune Hospital of Jilin University from April 2021 to November 2022.The supernatant was collected from the peripheral venous blood of the pregnant woman before termination of pregnancy,centrifuged and dispensed into Ep tubes and stored at-80℃.After centrifugation for 15 min,the supernatant was divided into 1.5ml Ep tubes and stored at-80 ℃.After delivery of the placenta by cesarean section,two pieces of placental tissue,approximately 1.0 cm*1.0 cm*1.0 cm in size,were taken from the non-hemorrhagic,calcified and necrotic areas.The placental tissues were rinsed with saline and blotted with sterile gauze,and one piece was placed in 10%formalin solution,and the other piece was placed in liquid nitrogen overnight and transferred to-80℃ refrigerator for freezing.The concentration of BNIP3 in serum was detected by enzyme-linked immunosorbent assay(ELISA).The expression level of BNIP3 protein in placental tissues was detected by protein blotting(Western-Blot)and immunohistochemistry.The pulsatility index(PI),resistance index(RI)and peak systolic flow velocity/end diastolic flow velocity(S/D)of the fetal umbilical artery were obtained by Voluson E10 abdominal ultrasonography and compared between the two groups.Results:1.Statistical analysis of the results of the ELISA experiment revealed that the concentration of BNIP3 in serum was reduced in the pre-eclampsia group compared with the normal control group,and the difference was statistically significant(P <0.0001).2.Statistical analysis of the results of Western-Blot experiments revealed that the expression of BNIP3 protein in placental tissues was reduced in the pre-eclampsia group compared with the normal control group,and the difference was statistically significant(P < 0.05).3.Analysis of the immunohistochemical staining results revealed that BNIP3 was significantly expressed in the syncytial trophoblast cells and only weakly expressed in the cytotrophoblast layer.It was highly expressed in the normal control group and lowly expressed in the preeclampsia group.The expression of BNIP3 in placental tissues was lower in the preeclampsia group compared with the normal control group,and the difference was statistically significant(P < 0.01).4.Fetal umbilical artery hemodynamic indexes were measured by abdominal color ultrasound Doppler,and the statistical analysis of the results showed that PI,RI,S/D and other umbilical artery flow parameters were higher in the pre-eclampsia group compared with the normal group,and the differences in PI were statistically significant(P < 0.01),and the differences in RI and S/D were statistically significant(P < 0.05).5.Correlation analysis showed that serum BNIP3 concentration was positively correlated with the relative expression level of BNIP3 protein in placental tissue.Fetal umbilical artery hemodynamic parameters PI,RI,S/D were negatively correlated with neonatal Apgar score and neonatal weight.Serum BNIP3 concentration and the relative expression of BNIP3 protein in placental tissue were negatively correlated with maternal blood pressure,and umbilical artery hemodynamic parameters PI,RI and S/D were positively correlated with maternal blood pressure.The concentration of BNIP3 in peripheral blood was negatively correlated with umbilical artery PI,RI and S/D.All the above were statistically significant(P < 0.05).There was no significant correlation between the relative expression of BNIP3 protein in placental tissue and umbilical artery hemodynamic parameters PI,RI and S/D(P > 0.05).Conclusion:1.BNIP3 expression in serum and placental tissues is correlated,and its reduced expression level in pre-eclamptic patients may be related to mitochondrial autophagy dysfunction and the development of the disease.The study of BNIP3 is expected to provide theoretical basis and potential therapeutic targets for clinical diagnosis and treatment of PE.2.The indicators of fetal umbilical arterial blood flow are correlated with neonatal body weight and neonatal Apgar score,which is of certain value for the evaluation of fetal status in PE patients,and can predict the outcome of pregnancy to a certain extent,providing a basis for clinical intervention and the choice of the time to terminate pregnancy.3.Whether there is a correlation between the expression level of mitophagy protein BNIP3 and fetal umbilical artery hemodynamics is still unclear,and further studies are needed.