Changes Of Lysophosphatidic Acid And Its Receptor-1in The Patients With Preeclampsia

Backgrounds and objectivesPreeclampsia(PE) is one of the specific diseases in pregnant women, leading to one of the important causes of maternal and perinatal morbidity and mortality.the etiology and pathogenesis has not yet been fully elucidated, currently placental ischemia\hypoxia and vascular are recognized as the pathological mechanisms of preeclampsia.Lysophosphatidic acid(LPA), is a lipid signaling molecules in the cell membrane, playing a variety of biological effects mainly through the G protein-coupled receptors (GPCRs).Three specific receptors of LPA is LPAR1-3as well as endothelial differentiation gene (Edg) Edg2\Edg4\Edg7. Recently studies are found that LPA can be secreted by many cells, but mainly by activated platelets (PLT), LPA can promote PLT aggregation and thrombus formation, and is related with coagulation abnormalities, endothelial damage, vascular sclerosis and so on.Studies indicate that the PLT counts in peripheral venous blood in patients with preeclampsia is significantly lower than that of the normal late pregnant women, the incidence of postpartum hemorrhage, DIC and neonatal mortality is significantly increased, but the cause is not yet unkown.Our previous studies found that the levels of plasma LPA with preeclampsia and the expressions of Edg4\Edg7protein in placental tissues with preeclampsia were significantly increased related to the severity of the disease;Another study shows that Edg4and Edg7are mainly related with cell proliferation and tumor genesis and development, while Edg2is mainly related with apoptosis, there is a phenomenon with preeclampsia that placental villus cell apoptosis.Whether the abnormal increase of LPA is related with PLT reduce and the expression of Edg2in placental tissues in the patients of preeclampsia, that is unknown now.In this study:(1) We detect plasma LPA levels and PLT counts with preeclampsia, analysis of the relationship between LPA and PLT;(2)We investigate the expressions of Edg2protein and mRNA in the placentas of patients with preeclampsia, analysising the relationship between the expression of Edg2and the development of preeclampsia.Material and Methods:1Clinical dataSamples were selected from November2011to May2012at the First Affiliated Hospital of Zhengzhou University hospitalized, selected40patients with preec-lampsia as the experimental group (of which20cases with mild preeclampsia and20cases with evere preeclampsias),.Diagnostic criteria for preeclampsia, with reference to Feng You-ji, is that the textbooks for institutions of higher learning"Obsetrics and Gynecology"(7th Edition) standard. Selected20cases of normal pregnancy as control group.All cases were got rid of the chronic hypertension, heart disease, kidney disease, inflammation disease and so on. the control group had no any pregnancy complications. All participants choose cesarean section, no premature rupture of membranes and signs of infection.2Experimental MethodsLevels of LPA in plasma were measured by biochemistry method. Determinatio-n PLT counts with five classification. Immunohistochemistry (SP method) and Reverse transcription-polymerase chain reaction (RT-PCR) were used to measure the protein and mRNA expressions of in placenta. 3Statistical analysisAll datas are analysed by the SPSS17.0statistical software, and results use (x±s), Categorical datas are analysed by chi-square test or calibration of the chi-square test. Measurement datas are analysed by one-way variance(normal sexual inspection and variance of all inspection), using LSD-t test in pairwise comparison between groups, Pearson correlation to statistical analysis.Statistical significance level is α=0.05or a’=0.0167, and P<0.05or P<0.0167is considered statistically significantly.Results:1.Plasma LPA levels with preeclampsia groups were significantly higher compaired with that of normal pregnancy women, and had a positive correlation with the condition of preeclampsia (P<0.05); The levels of PLT counts with preeclampsia groups were significantly lower than those of the control group;There is a negative correlation between levels of LPA in serum and PLT counts in peripheral venous blood.2.The expressions of Edg2protein can be detected in three groups, located in the cytoplasm and membrane of trophoblast cells and decidual cells.The expression rate of Edg2protein in placentas with preeclampsia were significantly higher than those from normal pregnant women(x21=10.101, P=0.001;x2=16.942, P<0.001) There was insignificance between the cases with mild preeclampsia and severe preeclampsia (P=0.225)3.The expression of Edg2mRNA in placenta with3groups were:normal control group (0.256±0.028), mild preeclampsia group(0.578±0.036) and severe preeclampsia group(0.955±0.039). Using analysis of variance (ANOVA) for comparison betwenn groups, the results showed that there were significant differences among the three groups (F=1961.276, P<0.001). The levels of mRNA expressions in the placentas from preeclampsia women were significantly higher than those from normal pregnant women, the levels of mRNA expressions in severe preeclamsia were significantly higher than those in normal pregnant women. Conclusions:1.Plasma levels of LPA with preeclampsia were significantly higher than those normal pregnant women and had a condition with the severity of the disease, indicating that LPA levels abnormal elevation could be associated with the occurrence of preeclampsia development.2.The levels of PLT counts with preeclampsia groups were significantly lower than those of the control group;There is a negative correlation between levels of LPA in serum and PLT counts in peripheral venous blood, indicating that the decrease of PLT counts may be related with LPA.3.The high expressions of Edg2protein and mRNA in placenta may be related to the pathogenesis of preeclampsia.