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The Expression And Significance Of Notch1 And Jagged1 In Placentas From Patients With Severe Preeclampsia

Posted on:2017-05-13Degree:MasterType:Thesis
Country:ChinaCandidate:S H XueFull Text:PDF
GTID:2284330485987124Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Preeclampsia is a kind of diseases during pregnancy and belongs to one of the five kinds of gestational hypertension disease. It is a kind of disease that is characterized with high blood pressure, urine protein and other organ dysfunctions after 20 weeks of gestation. According to the clinical symptoms preeclampsia can be divided into mild preeclampsia and severe preeclampsia. Severe preeclampsia can be divided into early-onset severe preeclampsia(ESPE) and late-onset severe preeclampsia(LSPE) according to gestational age. The morbidity of preeclampsia is about 9.4%. According to national maternal death reason survey reports, of the six major diseases, preeclampsia is located in the second place threating maternal life safety. The basic pathological change with preeclampsia patients is small vasospasm for the whole body. So blood supply of brain, heart, liver, kidney and other organs is limited, and vasospasm of placental reduce blood perfusion, eventually lead to placental abruption, fetal intrauterine growth restriction, and fetal death. However,the reason for preeclampsia is unknown. It may involve many factors about maternal,the placental and fetal. The failure of the trophocyte invasion, immune regulating disfunction, endothelial cell injury and nutritional factors can lead to preeclampsia.Due to the symptoms of preeclampsia can disappear quickly after placenta expulsion,therefore some scholars think that the formation of an anomalous placenta is in connection with preeclampsia. The placenta is primarily generated by trophocyte, andthe characteristics of trophocyte is very similar with the tumor cells in cellular proliferation and infiltration features. Many studies have shown that the abnormal cell invasion of trophocyte would influence the formation of placental, causing the placenta with shallow bed, may eventually lead to pathological pregnancy such as preeclampsia.Notch signaling pathway is a kind of transmembrane receptor protein family evolving conservatively. Some studies have found that the Notch signal influence the process of cell proliferation, differentiation, invasion and apoptosis. It also affect the invasion of the trophocyte. Classic Notch signaling pathways is produced by neighboring cells interaction between ligand and receptor activation.When Notch signaling pathways is activated, intracellular(NICD) will be released into the cell nucleus and transcript CSL, then NICD/CSL transcription complex formation activate HES, HEY, HERP, eventually make gene transcription inhibition or activation. Other studies have found Notch1 and Jagged1 in villi tissue and placenta during all time of pregnancy. It suggest that Notch1 and Jagged1 may play a role in placenta formation.This topic were to detect the difference expression of Notch1 and Jagged1 m RNA and protein in normal placenta tissues and severe preeclampsia placenta tissues and explore its relationship with severe preeclampsia. This may realise early intervention,improve the prognosis, provide new targets for clinical treatment.ObjectThe aims of this study were to analyze the changes in m RNA and protein levels of Notch1, Jagged1 in normal placenta tissues and severe preeclampsia placenta tissues by Real-time PCR and immunohistochemical, in order to explore whether Notch Signaling pathways influence placenta formation and play a role in preeclampsia.Materials and methods1 MaterialsAll the placenta tissues was choosen from December 2013 to December 2014 at the Third Affiliated Hospital of Zhengzhou University. There was a total of 60 patients with severe preeclampsia, including 30 patients with early-onset severe preeclampsia(ESPE) and 30 patients with late-onset severe preeclampsia(LSPE). The diagnose and classification of severe preeclampsia was based on the eighth edition of gynecology and obstetrics. At the same time 30 cases of normal full-term placenta tissues was choosen as the normal full-term group and 30 cases of preterm placenta tissues was choosen as preterm group because of cervical insufficiency or social factors. Above each group cases had no other medical and surgical complications and the pregnancy was a single pregnancy. This experiment was approved by our hospital ethics committee and specimen providers are informed consent.2 MethodsThe placental biopsies were collected within 15 minutes from the maternal side of the placenta and the whole process was strictly followed the principle of aseptic operation avoiding placental calcification and necrosis. Making the placenta tissues into 2 portions and cutting one portion into strips into tubes. Tubes can be temporarily stored in the liquid nitrogen, eventually into- 80℃ refrigerator. Another one portion was fixed with 10% formaldehyde after repeatedly rinsing with saline water,eventually used for immunohistochemical study. Using immunohistochemical method to detect the orientation and the relative expression of Notch1 and Jagged1 protein in placenta tissue. Another application of real-time fluorescent quantitative(RT-PCR)method was to detect Notch1 m RNA, Jagged1 m RNA expression in placenta of each group.3 Statistics analysisThe data used in this study was analysed using the SPSS version 19.0 software.The measurement of data was presented as mean ± standard deviation. Using two independent sample t-test to compare two groups of measuring data when conformed to normal distribution and homogeneity of variance; using nonparametric rank test to compare rank data. Significance was considered when P<0.05.Results1 General clinical data comparison among the four groupsIn the the late-onset severe preeclampsia group, normal full-term group, the early-onset severe preeclampsia group and the preterm group, the respectively maternal age were 29±4, 26±3, 28±4, 27±3; the gestational age were38.1±1.1,39.3±0.7, 27.3±0.6, 28.5±1.9; the systolic blood pressure were 150.89±7.86 mm Hg,117.50±5.32 mm Hg, 157.45±5.98 mm Hg, 113.34±6.37 mm Hg; the diastolic blood pressure were 93.54±4.56 mm Hg, 75.43±4.67 mm Hg, 107.67±5.73 mm Hg, 78.13±3.58 mm Hg. The age comparison among the four groups of pregnant women had no statistical significance(P > 0.05). The gestational age between the normal full-term group and the late-onset severe preeclampsia group had no statistical significance(P > 0.05). The gestational age between the the preterm group and the early-onset severe preeclampsia group had no statistical significance(P > 0.05). The systolic blood pressure and diastolic blood pressure in normal full-term group were lower than late onset severe preeclampsia(P < 0.05). The systolic blood pressure and diastolic blood pressure in the preterm group were lower than early-onset severe preeclampsia group(P < 0.05).2 The Notch1 m RNA expression in placenta of each groupOur results indicated that compared with the normal full-term group(1.0314 ±0.1536), the expression of Notch1 m RNA(0.9021 ± 0.1903) in late-onset severe preeclampsia group decreased.(P < 0.05). Compared with the preterm group(1.1076±0.1432), the expression of Notch1 m RNA(0.6832 ± 0.1345) in early-onset severe preeclampsia group decreased.(P < 0.05).3 The Jagged1 m RNA expression in placenta of each groupOur results indicated that compared with the normal full-term group(1.1257 ±0.1378), the expression of Jagged1 m RNA(0.7895 ± 0.1493) in late-onset severe preeclampsia group decreased.(P < 0.05). Compared with the preterm group(1.1065±0.1376), the expression of Jagged1 m RNA(0.6779 ± 0.1165) in early-onset severe preeclampsia group decreased.(P < 0.05).4 The expression of Notch1 protein in placenta of each groupNotch1 can be detected in all the four groups. It mainly exited in the cell cytoplasm and cell membrane of vascular endothelial cell and trophoblasts. Notch1 protein expressed in early-onset severe preeclampsia group was lower than the preterm group; Notch1 protein expressed in late-onset severe preeclampsia group was lower than the normal full-term group(P < 0.05).5 The expression of Jagged1 protein in placenta of each groupJagged1 can be detected in all the four groups. It mainly exited in the cell cytoplasm and cell membrane of vascular endothelial cell and trophoblasts. Jagged1 protein expressed in early-onset severe preeclampsia group was lower than the preterm group(P < 0.05); Jagged1 protein expressed in late-onset severe preeclampsia group was lower than the normal full-term group(P < 0.05).ConclusionsThe expressions of Notch1 and Jagged1 were decreased in severe preeclampsia placenta tissues. It suggested Notch signaling pathways especially Notch1, Jagged1 may participate in the occurrence of severe preeclampsia.
Keywords/Search Tags:severe preeclampsia, Notch1, Jagged1, trophoblast
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