The Research On The Relationship Between Adiponectin、pLGF And Preeclamsia

Preeclampsia(PE) is a pregnancy-specific disease and is characterized by new onset of hypertension(BP≥140/90 mm Hg) and proteinuria(urine protein≥0.3g/24 h or random urine protein(+))after 20 weeks of gestation. PE affects 5—8% of pregnancies internationally. Basic pathophysiological changes of the disease is general small vasospasm, endothelial injury and ischemia, The perfusion of whole system and each viscera decreases,leading to damage or mortality to maternal and fetal. The precise mechanisms of PE pathogenesis remain unknown.Because To alleviate the symptoms of the disease is catabatic or healing after delivery of placenta, some researchers call it "the placenta disease",but others believe it is a coefficient result of maternal, placenta,fetal and other factors. The current study provides the onset of preeclampsia may relate to insufficient remodeling of uterine spiral small artery, excessively activated inflammatory immune, vascular endothelial cell damage, genetic facto, nutrient deficiency and insulin resistance. Vascular endothelial dysfunction is the key link in the pathogenesis of preeclampsia. Endothelial dysfunction relates to vascular inflammation and the imbalance between angiogenic cytokines and anti-angiogenesis cytokines. Adiponectin, PLGF associate with angiogenesis and lesions.,and both express in trophocytes of placenta.This study aims to detec t t he expression of adiponectin and PLGF in placenta tissue in order to investigate their relationship with the oneset of preeclampsia and perinatal outcome.Adiponectin is a hormone protein, mainly being secreted by adipocyte in white adipose tissue.It has the effects of protecting endothelium, anti- inflammatory, anti-atherosclerosis and improve insulin resistance,and may play an important role in the pathogenesis of PE. Liver, cardiomyocytes,skeletal muscle, colon, salivary glands, placenta and pituitary express adiponectin at lower levels. Adiponectin performs its physiological effects mainly via Adipo R1 and Adipo R2 receptors. Adiponectin activates e NOS, increasing the levels of the vasodilator nitric oxide(NO) involving the occurrence of preeclampsia. Adiponectin level in preeclampsia is controversial. The base sequence of PLGF have a high homology with vascular endothelial growth factor(VEGF).The protein belongs to VEGF family and play a key role in angiopoiesis. Researches show that,PLGF promote S the proliferation of vascular endothelial cells, induing endothelial cell proliferation,migration and activation.Also it promotes the mononuclear cells and endothelial cells, increasing the permeability of endothelial cells. Placental growth factor(PLGF) is abundantly expressed in the placenta with primary sites of synthesis being trophoblast, correlating with a higher degree of trophoblast apoptosis. The normal development of fetai depends on complete the placental vasculature andabundant uteroplacental circulation. Hypoxicischemic results in imbalance of angiogenic factor in preeclampsia, hence we performed the following study to discuss the significance of adiponectin and PLGF in the development of severe preeclampsia.ObjectiveBy comparing the adiponectin m RNA and PLGFm RNA in normal group and severe preeclampsia group,evaluating their locations by IHC,this study aims to understand the relationship between their expression and perinatal outcome.Materials and methods1 MaterialsA total of 50 women with severe PE and 50 women with normal pregnancies were recruited from the Third Affiliated Hospital of Zhengzhou University between February and October in 2014. The criteria for diagnosis of severe PE were strictly based on the American Congress of Obstetricians and Gynecologists criteria(2002). All subjects were ruled out chronic hypertension, diabetes, kidney disease, and polycystic ovary syndrome, fetal abnormalities, and multiple pregnancy.This study was approved by the Human Ethics Committees of the Third Affiliated Hospital of Zhengzhou University. Informed consent was obtained from all the women participating in the study.2 MethodsAs soon as possible after delivery(within 15 minutes), 2 samples of placenta, 1×1×1cm in size and 0.5×0.5×0.5cm in size, were taken, both from the central portion of the maternal surface. Blood in the tissues was removed with normal saline. A portion of the sample was fixed in 10% formalin, paraffin embedding, slice(4 microns) for IHC, and the other portion of the sample was immediately frozen in liquid nitrogen and stored at-80°C. Areas with hemorrhage,infarction, and calcification were avoided when collecting the samples. Using the Real- time PCR technology to detect adiponectin and PLGFm RNA expression in both two groups. Using immunohistochemistry to locate adiponectin and PLGF in both preeclampsia group and normal group.3 Statistics analysisAll statistical analyses were performed using SPSS 19.0 softwa-re. Using mean ± standard deviation(SD) to express quantitative dates.Using eithe-r unpaired t test(for parametric data) or rank sum test(for non-parametric data) to compare two groups. Relativity analysi-s used Spearman correlation analysis. Difference-s were considered to be statistically signific-ant when P < 0.05.Results1 The maternal general datas in both severe preeclampsia group and control group.Coparing the median age and pregnancy body mass index(BMI) severe bpth in preeclampsia group and normal control group women, the differences were statistically significant(P < 0.05).The pregnant weeks is different between the two groups(P < 0.05); The neonatal average weight is similar between the two groups were statistically significant different.( 2144.2±656.13 g 3349.8±386.36 g, p < 0.05); The difference of the neonatal height were statistically significant(43.68±3.88 cm, 51.24±2.39 cm, p < 0.05);Two groups of the placenta weight were 378.52 + /- 56.54 g, 575.20 + /- 90.63 g, The difference of the placenta weight in both groups were statistically significant(378.52±56.54 g, 378.52±56.54 g p < 0.05).2 The Adiponectin,PLGF m RNA expression in placenta of both groups.2.1 Adiponectin m RNA expression in severe preeclampsia group and the control groupAdiponectin m RNA are expressed in the two groups of placental tissue, relative expression of adiponectin m RNA in severe preeclampsia placenta expression is higher than normal group(4.18±1.80, 1.00±0.51) the difference was statistically significant.(P<0.05)2.2 The PLGF m RNA expression in placenta of both groups.PLGFm RNA are expressed in the placenta of two groups The PLGFm RNA relative expression in severe preeclampsia is lower than the normal control group(1.00±0.50, 3.19±1.09), the difference was statistically significant, P < 0.05).2.3 Localization of Adiponectin and PLGF protein expression in the placenta of severe preeclampsia group and normal control group.This study found that adiponectin and PLGF are expressed in the two groups of placental tissue, adiponectin protein expressed in severe preeclampsia group is significantly higher than normal group(P < 0.05), protein) The staining intensity of PLGF in placenta tissue of severe preeclampsia group was obviously lower than that of normal control group(P < 0.05).2.4 Relativity analysisThere is negative relationship between adiponectin m RNA level and PLGF m RNA level in the placental tissue of the severe PE group(r=-0.575,P<0.05); The adiponectin m RNA relativ-e expression quantity negativel-y correlated with neonatal height(r=-0.580,P<0.05),positively correlate-ng with maternal BMI(r=0.261,P<0.05),and have no correlation with maternal age(r=0.242,P>0.05); The PLGF m RNA relative expression quantity positively correlated with neonatal height(r=0.625,P<0.05),negatively correlating with maternal BMI(r=-0.374, P<0.05),and have no correlation with maternal age(r=0-0.146,P>0.05).Conclusion1. Adiponcetin m RNA and adiponectin protein expressioin in sever-e preeelamsia placenta tiss-ue was higher than the control group,PLGF m RNA and PLGF protein expressioin in severe preeelamsia placenta tissue was lower than the control group,suggesting that adiponectin and PLGF may involved in the pathogenesis of severe preeclampsia.2. Adiponectin and PLGF in negative correlation in severe preeclampsia, suggesting they may nfluence the occurrence of severe preeclampsia development in the severe preeclampsia. The correlation between adiponectin, PLGF and suggests both of them were related to weight gain in pregnancy; The c-orrelation between adiponectin, PLGF and neonatal weight suggests both of them were relate to perinatal outcome of sever-e preeclampsia.