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Study On The Correlation Between SFlt-1、HIF-1α、Caspase-3and The Idiopathic Fetal Growth Restriction

Posted on:2013-04-27Degree:MasterType:Thesis
Country:ChinaCandidate:P P LiuFull Text:PDF
GTID:2234330371975988Subject:Gynecology
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BackgroundFetal growth restriction (FGR) is usually defined as a birth weight below the two standard or the10th percentile number of deviation of the average weight. It not only has an influence in the growth and development of the fetus in utero, but also affects the physical and mental development of the baby. The aetiological agent of FGR was divided into three parts include maternal factor, fetal factor and placental factor, but it still had some etiology we did not know. So we called idiopathic fetal growth restriction (IFGR). In recent years, along with the development of the study of the etiology in microvascular, the people had been concerned about the angiogenesis factors which was formed by the placental invasion villous. The animal study has indicated that it has a very closely relationship between the aetiological agent of IFGR and the microvascular factors which was invasion by the trophoblastic of placental. And it display that the decrease in the number of placental villous capillary or structure dysfunction of it. The reason may be due to that in the early time of the development of embryonic and the formation of placenta, trophoblast invasion, differentiation, and the abnormal maturation in the relatively hypoxic intrauterine environment, and the formation and function of placental blood vessel were affected, then appeared a series of complications which had impacted on pregnancy. This study is on the anomalies formation of placental vessels which caused by the lack of oxygen in placental, All of these are to have an early prediction on IFGR and provide a treatment evaluation for it. Hypoxia inducible factor-la (HIF-la), an important transcription factor, regulates many factors including the change of cell intrinsic in the hypoxic environment. This factor regulated VEGF, sFlt-1, EPO, leptin and endothelin, which affect the formation of blood vessels, also maintain the vascular structure and function. Soluble Vascular Endothelial Growth Factor Receptor (sFlt-1), who combined with specific ligand of VEGF, will play a direct role in angiogenesis, is also regulated by HIF-la which express in the hypoxic environment. Caspase protein-3(caspase-3), a core protein of the protease cascade, regulated the process of the apoptosis of extravillous trophoblast cells in placental. And its overexpression can make the decrease of the new vessels in the early time of the development of embryonic and the formation of placenta. Now, it was unknown that whether the three factors (HIF-la, caspase-3and sFlt-1) had a correlation with the pathogenesis mechanism of IFGR.ObjectiveTo study on the expression of HIF-la, caspase-3in placenta and the expression of sFlt-1in the maternal and cord serum in the IFGR group and the control group, and discuss the function and the correlation among them in the pathogenesis mechanism of IFGR.Methods1. MaterialWe selected the thirty pregnant women with IFGR who chose cesarean section to terminate the pregnancy in the obstetric ward of the Third Affiliated Hospital of Zhengzhou University during July2010and July2011as the experimental group, and others who chose cesarean section to terminate the pregnancy because of pelvis and social factors as normal control group, also30cases. The diagnosis of IFGR is the2nd edition of Obstetrics and Gynaecology which edited by Youji Feng.2. Methods 2.1The methods of experimental:We use immunohistochemistry to detect the expression of HIF-la and caspase-3in placentas in two groups, and use ELISA to detect the expression of sFlt-1in the maternal and cord serum.2.2The methods of statistical:We use the SPSS13.0software to statistical analysis. All of the experimental data were described with mean±standard(x±s). Comparison with the two means used T test. The linear correlation (Pearson) analysis was used to determine the relationship of two factors correlation analysis. Statistically significant level was considered as "a=0.05".Results1. The compare of general clinical data in the IFGR group and the control group.1.1The difference is not statistically significant in the general clinical data of pregnant women between the normal group and the IFGR group (p>0.05).1.2The comparsion of basic information in neonatal:the weight of neonatal in IFGR group is (2212±212)g which is lower than it in the normal group. The Apger scores of the neonatal in IFGR group are lower than that in the control group, and the difference have statistically significant (p<0.05).2. The comparsion of the expression of caspase-3, HIF-la in placental tissue in the IFGR group and the control group.In two groups there have the positive expression of HIF-la, caspase-3in the placental tissue in the pregnant women, and they are expressed on the cell membrane and cytoplasm and they are mainly concentrated in the placental syncytiotrophoblast, extravillous trophoblast cells, the mesenchyma of chorionic and around of the vascular intima which are observed under the microscope.The expression of HIF-la in placental tissue is higher in IFGR group than it in normal group, the difference have statistically significant (p<0.05). The expression of caspase-3in placental tissue is higher in IFGR group than it in normal group, the difference have statistically significant (p<0.05).3. The comparsion of the expression of sFlt-1in the serum in the IFGR group and the control group.The sFlt-1in the serum of pregnancy women in the IFGR group is higher expression than the control group, the difference have statistically significant (p<0.05). The sFlt-1in the serum of umbilical in the IFGR group is higher expression than the control group, the difference have statistically significant (p<0.05). In the IFGR group, the sFlt-1in the serum of umbilical is higher expression than in the serum of pregnancy women, the difference have statistically significant (p<0.05).4. The correlation analysis among sFlt-1, HIF-1α, and caspase-3protein in the IFGR group4.1In the IFGR group:the expression level of sFlt-1in the umbilical and the expression level of HIF-1α in placental tissue have positive correlation (P<0.05); the expression level of sFlt-1in the maternal and the expression level of HIF-1α in placental tissue have positive correlation (p<0.05).4.2In the IFGR group:the expression level of sFlt-1in the umbilical and the expression level of caspase-3in placental tissue have positive correlation (p<0.05); the expression level of sFlt-1in the maternal and the expression level of caspase-3in placental tissue have positive correlation (p<0.05).4.3In the IFGR group:the expression level of HIF-1α in placental tissue and the expression level of caspase-3in placental tissue have positive correlation (p<0.05). No correlation in the control group.4.4The expression level of sFlt-1in the umbilical blood and maternal blood in the IFGR group have positive correlation (p<0.05).Conclusions1.The expression of HIF-1α, caspase-3were observed in the placental tissue and the expression level of sFlt-1in the umbilical and maternal in IFGR group may be related with the pathogenesis mechanism of IFGR。2.The factor HIF-1α may regulate the expression of caspase-3and sFlt-1that may be influence the growth of fetus in utero.
Keywords/Search Tags:soluble Fms-Like Tyrosine kinase-1(sFlt-1), cysteinyl aspartatespecific proteinase-3(caspase-3), Hypoxia-Inducible Ffactor-1(HIF-1α), IdiopathicFetal Growth Restriction (IFGR)
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