Relationship Between LncRNA MVIH,AP-1 And Spiral Arteries Remodeling In Placenta Of Severe Preeclampsia

Background and ObjectivePreeclampsia(PE),as a unique clinical syndrome during pregnancy,is characterized by abnormalities of placenta and maternal vascular endothelium,and can cause multiple organ dysfunctions in the whole body of the pregnant women.The prevalence of pregnancies among pregnant women in the world is 5%-8%,which is very harmful to mothers and children,but its pathogenesis remains unclear.One of the currently recognized major inducements is the lack of revascularization of the placental spiral arteries.In the process of placenta formation in preeclampsia,shallow infiltration of trophoblasts can cause re-injection of spiral arteries,which in turn leads to decreased placental blood flow,leading to a series of preeclampsia performance.Preeclampsia is divided into mild and severe,severe clinical manifestations of preeclampsia are more serious,prone to maternal systemic organ dysfunction or fetal complications,a serious threat to maternal and fetal safety.Long noncoding RNA associated with microvascular invasion in hepatic carcinoma(lncRNA MVIH)is a long-chain non-coding RNA associated with tumor microvascular invasion.It can increase the invasive ability of microvessels and promote the formation of new blood vessels.Activator protein-1(AP-1)is a type of transcription factor that is induced by extracellular stimulation and is present in eukaryotic cells.AP-1 regulates the proliferation and differentiation of trophoblast cells.Therefore,this study examined the expression of lncRNA MVIH and AP-1 in severe preeclampsia and normal placental tissue,and the changes in wall thickness and lumen area of placental spiral arteries,the correlation between lncRNA MVIH,AP-1 and placental spiral arterial changes was analyzed to investigate the role of lncRNA MVIH and AP-1 in placental spiral arterial remodeling during severe preeclampsia.Materials and Methods1.Study populationSelect from July 2016 to January 2017,35 cases(experimental group)of severe preeclampsia pregnant women hospitalized for cesarean section in the Third Affiliated Hospital of Zhengzhou University.In addition,33 normal healthy pregnant women(control group)were selected and delivered for caesarean section due to pelvic abnormalities,breech presentations,and other reasons.Both groups of pregnant women were singleton pregnancies,naturally conceived,and had no previous history of hypertension,diabetes,kidney disease,heart disease,and hyperthyroidism;they excluded congenital inherited diseases,coagulopathy,genital malformations,and other pregnancy complications.2.Methods2.1.Placenta specimen collectionThe placental specimens taken were within 15 minutes after the placenta was delivered.The uterus wall was used as the placenta attachment position,the placenta was peeled off,the placenta bed was exposed,and in the central basal membrane area of the mother's face,the tissue with a size of about 1.5 cm×1.0 cm×0.5 cm was cut out.After dehydration of glutaraldehyde,the tissue was placed in a refrigerator at 4°C.Store for scanning electron microscopy to observe changes in spiral arteries.In addition,four tissues(1.0 mm in diameter,1.0 mm in diameter and 1.0 cm in diameter)were removed from the central quadrant of the mother of the placenta and washed in phosphate-buffered saline(PBS).After blood was placed in liquid nitrogen,and then transferred to-80°C refrigerator for future use.2.2.Scanning electron microscope was used to observe and measure the wall thickness and luminal area of placenta spiral arteries in both groups.2.3.Real-time fluorescence quantitative PCR was used to detect the expression of MVIH mRNA in the placenta of pregnant women.2.4.Western blotting was used to detect the expression of AP-1 protein in the placenta of two groups of pregnant women.3.Statistical processingStatistical Statistical analysis using SPSS21.0 statistical software,real-time fluorescence quantitative PCR results using 2~-??Ct??Ct analysis,measurement data using mean±SD,in line with the normal distribution of data for the two groups of independent Sample t test,which does not meet the normal distribution data using rank sum test,the correlation analysis of two variables using the pearson correlation analysis.The test level is?=0.05.Results1.Comparison of two general clinical data There was no significant difference in the ages,termination of gestational weeks and BMI before delivery between the control group and the experimental group(P>0.05).The systolic blood pressure and diastolic blood pressure of the experimental group were higher than those of the control group,and the differences were statistically significant.Significance(P<0.05);The birth weight of newborns in the experimental group was lower than that of the control group(P<0.05).No urinary protein was detected in the control group,and the24-hour urinary protein of the experimental group was significantly increased.2.Placenta spiral wall thickness and lumen area of two groups comparedThe average wall thickness of the spiral arteries in the control group was(101.92±8.60)?m and the mean lumen area was(189.30±26.78)?m~2.The mean wall thickness of the experimental group was(117.85±8.94)?m and the average luminal area was(139.85±27.97)?m~2.The average wall thickness and average luminal area of the two groups were compared,the difference was statistically significant(P<0.05).3.Comparison of MVIH mRNA Expression Levels in Placenta Tissues of Two Groups Real-time PCR showed that the relative expression levels of MVIH mRNA in control and experimental groups were(0.99±0.17)and(0.34±0.05),respectively.The experimental group was lower than the control group,the difference was statistically significant(P<0.05).4.Comparison of AP-1 protein expression in placental tissue between two groups Western blotting showed that the relative expression levels of AP-1 protein in control and experimental groups were(0.18±0.03)and(0.59±0.11),respectively.The experimental group than the control group,the difference was statistically significant(P<0.05).5.Correlation analysis MVIH mRNA expression was negatively correlated with vessel wall thickness(r=-0.617,P<0.05),positively correlated with luminal area(r=0.592,P<0.05),and negatively correlated with AP-1(r=-0.874,P<0.05),the difference was statistically significant.There was a positive correlation between AP-1protein expression and wall thickness(r=0.579,P<0.05)and a negative correlation with lumen area(r=-0.630,P<0.05),the difference was statistically significant.ConclusionsThe lncRNAs MVIH and AP-1 may participate in the pathogenesis of severe preeclampsia by regulating the process of placental spiral arteries remodeling.