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Study On The Role Of HIF-1 NF-κBp65 And HSP70 In Hypertensive Disorders In Pregnancy

Posted on:2010-06-11Degree:MasterType:Thesis
Country:ChinaCandidate:L Q ZhangFull Text:PDF
GTID:2144360275469822Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Objective: Hypertensive disorders in pregnancy is the peculiar disease in pregnancy, it is one of the main causes for the death of pregnancies and neonates, however, the etiology of hypertensive disorders in pregnancy remains unclear. At present, the muscle of uterus was invasived by abnormality trophoblast, immunity mechanism, injury of maternal vascular endothelium are thought the important reasons. The invasion of abnormality trophoblast makes atherosclerosis of uterine spiral arteries, which cause insufficient placenta perfusion. At last, placenta short of oxygen and blood, Hypoxia inducible factor-1 alpha (HIF-1) is an important transcriptive factor that regulates genes involved in angiogenesis, cellular oxygen balance and energy metablossom. Activation of transcription factor nuclear factor kappa B (NF-κB) which includes NF-κB/P65 and NF-κB/P50 was found in 1986. It has been proved to play an important role in immunity, Burning disease reaction, growth of cell and apoptosis and so on. Heat shock protein 70 (HSP70) are expressed increases significantly when biology are stimulated by some damaged factors. HSP70 called"molecular partner"can combine other relative proteins into complex to take part in the folding,assembling,transporting,degrading of these proteins by the forming or dissociating of the complex, and it also can protect ourselves from material hurt. Through studying characteristics and relativity among HIF-1 NF-κBp65 and HSP70 in placenta of hypertensive disorders in pregnancy, we hope provide the evidence of experiment theories for clinical treatment.Methods: Ninety women with hyptensive disorders in pregnancy(30 gestational hyptension, 30 light preeclampsia, 30 severe preeclampsia)and 40 women with normal pregnancy were recruited the fourth affiliated hospital of Hebei medical university as study group and control group. Respectively, the two groups excepted other disease were maternal age, party gestational age. Sample collecting: About lcm3 placental tissues were collected from the pregnant women after the placenta was deliveried. Use axenic 0.9% sodium chloride to wash it and fix it with formaldehyde. Use H and E method and immunohistochemical method to determine the level of HIF-1 NF-κBp65 and HSP70 in placenta. The data was analyzed by SPSS13.0 software wrap, Chi-Square Test and Spearman grade relation analysis are involved. Statistically significant level was considered as"alpha equals 0.05".Results: 1 there were no statistical difference between control and preeclampsia group in age and gestational age(p>0.05).2 Immunohistochemical staining for HIF-1αprotein was located at the cytoplasm and nucleus of the cytotrophoblast as well as extra villous trophoblastic cells, some weak signals were showed in the cytotrophoblast. Immunohistochemical staining for HIF-1αprotein was located at the cytoplasm and nucleus of the cytotrophpblast as well as syneytiotrophoblast, Immunohistochemical staining in the cytotrophpblast showed weaker than syneytiotrophoblast. The expression of HIF-1αprotein in trophocyte showed significant higher in every group of hypertensive disorders in pregnancy(positive rate=78%) than in control group(positive rate=30%): the expression in gestational hypertension group is higher than that in control group(x~2= 3.889, P=0.049<0.05).The expression in light preeclampsia group is higher than that in control group(x~2=17.157, P=0.000<0.05). The expression in severe preeclampsia group is higher than that in control group(x~2=35.00, P=0.000<0.05).The expression of HIF-1αprotein showed significances correlated with the degree of differentiation: the expression in gestational hypertension group is lower than that in light preeclampsia group(x~2=4.800, P=0.028<0.05).The expression in light preeclampsia group is lower than that in severe preeclampsia group(x~2= 6.667, P=0.010<0.05).3 Immunohistochemical staining for NF-κBp6 protein was located at the cytoplasm and nucleus of the cytotrophoblast as well as extra villous trophoblastic cells, some weak signals were showed in the cytotrophoblast. The expression of NF-κBp65 protein in trophocyte showed significant higher in every group of hypertensive disorders in pregnancy(positive rate=79%) than in control group(positive rate=33%): the expression in gestational hypertension group is higher than that in control group(x~2= 4.088, P=0.043<0.05). The expression in light preeclampsia group is higher than that in control group(x~2=15.52, P= 0.000<0.05).The expression in severe preeclampsia group is higher than that in control group(x~2=32.95, P=0.000<0.05).The expression of NF-κBp6 protein showed significances correlated with the degree of differentiation: the expression in gestation hypertension group is lower than that in light preeclampsia group(x~2=3.774, P=0.052>0.055).The expression in light preeclampsia group is lower than that in severe preeclampsia group(x~2=6.667, P=0.010<0.05).4 Immunohistochemical staining for HSP70 protein was located at the cytoplasm of the cytotrophoblast as well as extra villous trophoblastic cells. The expression of HSP70 protein in trophocyte showed significant higher in every group of hypertensive disorders in pregnancy(positive rate=72%) than in control group(positive rate=45%): the expression in gestational hypertension group is higher than that in control group, but it isn't Statistically significant (P>0.05). The expression in light preeclampsia group is higher than that in control group(x~2= 5.619, P=0.018<0.05).The expression in severe preeclampsia group is higher than that in control group(x~2=20.74, P= 0.000<0.05). The expression of HSP70 protein showed significances correlated with the degree of differentiation: the expression in gestational hypertension group is lower than that in light preeclampsia group(x~2=4.444, P=0.035<0.0). The expression in light preeclampsia group is lower than that in severe preeclampsia group(x~2= 6.405, P= 0.026<0.05).5 The HIF-1α,NF-κBp65 and HSP70 in the placental was activated. At the same time, the expression degree of HIF-1α,NF-κBp65 and HSP70 was positive correlate to the degree of hypertensive disorders in pregnancy. In addition, they were positive correlate to each other.Conclusion: 1 The abnormal expression of HIF-1α,NF-κBp65,HSP70 were more severity accompanied with the progress of hypertensive disorders in pregnancy, which was positive correlate to pathogenetic condition degree of the disease and was the importance season possibility.2 High expression of HIF-1αwhich was induced by anoxia may make NF-κBp65 express highly through controlling inflammatory factor, and the activation of NF-κBp65 increase inflammatory factor which hurt trophoblast seriously. HIF-1α,and NF-κBp65 are together related to the pathogenesis of hypertensive disorders in pregnancy and typical pathological change in placenta.3 The activation of HIF-1αprotect cells avoiding hurt in placenta of hypertensive disorders in pregnancy, however, it need study that HIF-1a develop condition of the disease.4 Two of HIF-1α,NF-κBp65,HSP70 are positive correlate to each other, which contact closely and effect each other. We will get the accurate mechanism of hypertensive disorders in pregnancy by further research in the molecular biology level, which will provide theories evidence of earlier period prevention and treatment.
Keywords/Search Tags:hypoxia inducible factor-1(HIF-1), nuclear factor-κB(NF-κB), heat shock protein 70(HSP70), hypertensive disorders in pregnancy, preeclampsia
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