The Expressions Of HIF-1α,PHD1,2 And FIH-1 In Placenta And Their Effects In The Pathogenesis Of Pre-eclampsia

AbstractObjective:Pre-eclampsia is one of the pregnancy-specific disease that affects the health of maternity pantient and neonate,its etiology and pathogenesis not entirely clearly.Throught entensive study suggest:inadequate invasion and remodeling of spiral arteries patyiculatly within the myometrium by extravillous cytotrophoblasts are believed to contribute to the disease pathogenesis,In recent years,research indicates that Hypoxia inducible factor has been implicated in the regulation of cyrotrophoblast stem cell proliferation,differentiation and invasion,And with a activation and regulatory function is HIF-1αsubunit.The oxygen sensor- Prolyl hydroxylase domain-containing protein 1,2(PHD1,2) and Factor inhibiting HIF-1α(FIH-1), respectively play a role in protein expression and transcriptional activity. Immunohistochemistry methods analysis were used to detect the HIF-1α,PHD1,2 and FIH-1 protein expression in placentas of normal pregnant(NP)women and pre-eclamptic(PE) women and to dicuss their effects in the pathogenesis of preeclampsia。MethodsImmunohistochemistry method was used for 10 placental samples of mild and 28 placental samples of severe preeclampsia and 24 normal placental samples to investigate the expression of HIF-1α,PHD1,2 and FIH-1 proteins in placenta tissues.Results1.Protein expression of HIF-1αin pre-eclamptic and normal placentaImmunohistochemical staining for HIF-1αprotein was location at the trophoblast cell.The majority of the stainting was in the syncytiotrophoblast,some weak signals were showed in the cytotrophoblast.The staining was both cytoplasmic and nuclear, wIth the former being particularly intense.In addition,Immunohistochemical staining for HIF-1αprotein was rarely in villous stroman and in the fetoplacental vascular endothelium.The expression of HIF-1αprotein in severe preeclampsia group is higher than that in mild pre-eclampsia group,Statistically significant differences(P＜0.01), and the mild pre-eclampsia group is highter than that in control group,Statistically significant differences(P＜0.01).2.Protein expression of PHD1 in normal and pre-eclamptic placenta.Immunohistochemical staining for PHD1 protein was location at the cytotrophoblast,syneytiotrophoblast,villous stroman and the fetoplacental vascular endothelium.The staining was predominantly in cytoplasmic.The expression of PHD1 protein showed significant lower in severe pre-eclampsia group than in control group, Statistically significant differences(P＜0.01).The expression in severe preeclampsia group was compared with in mild pre-eclampsia group,Statistically significant differences(P＞0.05),and the mild pre-eclampsia group was compared with in control group,Statistically significant differences(P＞0.05).3.Protein expression of PHD2 in normal and pre-eclamptic placenta.Immunohistochemical staining for PHD2 protein was location at the trophoblast cell.The majority of the stainting was in the cytotrophoblast,and also can be found in villous stroman and the fetoplacental vascular endothelium.The staining was both cytoplasmic and nuclear,with the former being particularly intense.The expression of PHD2 protein showed significant higher in pre-eclampsia severe group than in control group,Statis-tically significant differences(P＜0.01).The expression in preeclampsia severe group is higher than that in mild pre-eclampsia group,Statistically significant differences(P＜0.01),and the mild pre-eclampsia group was compared with control group,Statistically significant differences(P＞0.05).4.Protein expression of FIH-1 in normal and pre-eclamptic placenta.Immunohistochemical staining for FIH-1 protein was location at the trophoblast cell.The majority of the stainting was in the cytotrophoblast.The staining was both in cytoplasmic and nuclear.The staining can rarely be found in villous stroman and the fetopacental vascular endothelium.The expression of FIH-1 protein showed significant lower in severe pre-eclampsia group than in control group,Statistically significant differences(P＜0.05).The expression in severe pre-eclampsia group was compared with mild pre-eclampsia group,Statistically significant differences(P＞0.05), and the mild pre-eclampsia group was compared with control group,Statistically significant differences(P＞0.05).5.Correlation analysis:in the placenta of pre-eclampsia group the expression of HIF-1αwas positive correlation with that of PHD2:correlation coefficient(r=0.554,P＜0.01);Meanwhile,there was negative correlation with that of PHD1 and FIH-1:correlation coefficient(r=-0.631,P＜0.01 and r=-0.498,P＜0.01).ConclusionProtein expression of HIF-la,PHD2 is highter in severe pre-eclamptic placenta that in normal placenta,but protein expression of PHD1 and FIH-1 is significant lower in severe pre-eclampsia than that in normal placenta,HIF-1αwas positive correlation with PHD1,Meanwhile was negative correlation with with PHD1 and FIH-1.So PHD1,PHD2 and FIH-1 might involve in the pathogenesis of pre-eclampsia through inhibiting the HIF-1α.