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Expression And Significance Of The Receptor Of Advanced Glycation End Products,P-selectin In The Placenta Of Preeclampsia

Posted on:2012-09-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y M LiFull Text:PDF
GTID:2214330338456889Subject:Obstetrics and gynecology
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Background and ObjectivePreeclampsia is one of the hypertensive disorders in pregnancy, it is a special disease in pregnancy, also is an important reason of the maternal and her son around to death. So it is the research hotspot for many years in local or overseas. The causes and mechanism of this disease are so complex that we can not fully clarify them now. Recently, inflammatory reaction has been heeded gradually in mechanism of preeclampsia. Many kinds of influencing factors can causes the placenta oxidative stress, and the placenta releases the massive inflammatory factors, and inducing the occurrence of inflammation and the blood vessel endothelial cell suffers injury, this mechanism receives many scholars of the present domestic and foreign approval.P-selectin is called the typical intercellular adhesion molecule elements in inflammatory reaction. It is a key factor in the inflammatory reaction starting and maintaining an inflammatory state. P-selectin is main membership of family choice in cell adhesion molecules (cAMs), and usually stored in the nappi cells secretory granules, stationary particles and the density of the particles of platelet. When it was exciting by, blood enzymes and calciumions carrier A23187, anoxia and other incentives and the oxidizing, it's expression rapid increases and be participated in the inflammatory reaction. Study shows that, during pregnancy, P-selectin expresses in the cells of born interface, when the expression's level increases, it will activate platelet, release massive platelet activation factor(PAF),enhance inflammatory reaction, activate multinucleated giant cell (MGC)) and damage the structure and integrity of Nappi cell, causes tiny blood clot jam and contraction of the vessels collection function, finally causes the blood to the placenta reduced and impact on the growing fetus. It is an important pathological procession of preeclampsia.The receptor of advanced glycation end products (RAGE) is a multi-ligand member of the immunoglobulin super family, and is a single across membrane fragments receptor, Human's RAGE gene in 6p21.3, and have an effect of residues 383. As a signal transmits receptor, RAGE/ligand interaction activate several signal transduction pathways, such as P21Ras,mitogen-activated protein kinaes(MAPK),cdc42/rac,Janus kinase/signal transducer and activated of transcription(JAK/STAT),nuclear factor-KB,induces the disorders of the cells function and be participated in the inflammatory reaction. Cooke has reported that the normal pregnant woman have expression of RAGE in the placenta,womb vascular bed, and the expression of preeclampsia significantly rise, it's ligands-calgranulin also obviously rise in the preeclampsia, It hints that RAGE may be participated in the pathological process procession of preeclampsia.We use RT-PCR method and immunohistochemistry (SP method) to detect the expression of RAGE and P-selectin mRNA in placenta tissue from normal term pregnant and the patients of preeclampsia, and research their expression and distribution in normal pregnant women and patients of preeclampsia, so we can explore their relevance in the occurrence and development of preeclampsia.Materials and Methods1 Clinical cases dateSamples take from May 2009 to December 2009 in the First Affiliated Hospital of Zhen Zhou University, Obstetrics and Gynecology.40 patients with preeclampsia (mild preeclampsia group20case, severe preeclampsia group20case) are research objects, with an average age of 29.5±4.8 years, the week on average 36.5±2.4 week, and pregnancy times is 2.3±0.4 time; Compared group are 30 women requested termination of normal pregnancy, with an average age of 27.2±2.4 years, the week on average38.5±4.6week, and pregnancy times is 2.1±0.6 time. The normal pregnancy and mild or severe preeclampsia group have no statistically significant difference in general information about the height,age,weight and the pregnant week act(p=0.10).All the subjects have no hypertension,diabetes,kidney problems,habitual abortion history,the immunity disease and other medical history recently, and all the subjects without other complications and complications of pregnancy. The diagnostic criteria are referenced the standard of gynecology and obstetrics (eight year. the second edition). Delivery mode is operation, and the birth of the vagina not included.2 Experimental methodsRAGE and P-selectin mRNA was detected of the placenta tissue in patients with normal pregnancy and preeclampsia using PT-PCR method. RAGE protein and P-selectin protein were detected in the placenta tissue of patients with normal pregnancy and preeclampsia by immunohistochemistry method.3 Statistical analysisThe data were analyzed by SPSS 16.0 statistical software. The relative expression of RAGE,P-selectin in placenta tissue were analyzed by single factor analysis and LSD-t inspection, Spearman correlation analysis was used to analyze the relevance. The test standard was a=0.05..Results1. Immunohistochemistry results:The RAGE protein was mainly expressed in the cytoplasm and membrane of trophoblast cells, but there was a small amount in the vascular endothelial cells. P-selectin was mainly expressed in the syncytiotrophoblast cells, vascular endothelial cells and interstitial cells. The expression of RAGE and P-selectin in preeclampsia placenta tissue (mild preeclampsia was121.10±13.01,125.86±9.13 and server preeclampsia was 152.06±12.31,161.09±11.37) was higher than that of normal pregnancy (101.08±6.72,106.54±9.53) and the levels of severe preeclampsia were higher than those with mild preeclampsia (FRAGE=250.125, Fp-selecting=274.044, P<0.01)2. RT-PCR results:Expression of RAGE mRNA and P-selectin mRNA in the placenta tissue of preeclampsia group(mild preeclampsia was0.455±0.059,0.417±0.052 and server preeclampsia was 0.863±0.097,0.763±0.049) was significantly higher compared with that of control group (0.234±0.019,0.318±0.026), the levels of severe preeclampsia were higher than those with mild PE (FRAGE=624.55, FP-selecting=708.35, P<0.05).3. Relevance analysis revealed:There is a positive correlation between them in the protein expression of preeclampsia (rmild=0.513, rseverse=0.796, P<0.05) and in the mRNA expression of preeclampsia(rmild=0.607, rseverse=0.796, P<0.05)Conclusion1. In this study we found that RAGE protein and mRNA expression in the preeclampsia was higher than the normal preganacy. It hints that RAGE may have some effects in the occurrence and development of preeclampsia.2. We research discovered that P-selectin protein and mRNA expression in the preeclampsia group was higher than that normal pregnancy group. It hints that the high level expression of P-selectin may have a closely relation with the occurrence and development of preeclampsia.3. Not normal expression of RAGE,P-selectin may be participated in the procession of preeclampsia. They have a positive correlation in the procession. So, detects the expression of RAGE,P-selectin in the placenta tissue together will may become the new indicators in diagnosis, the inspection and prognostic of preeclampsia.
Keywords/Search Tags:preeclampsia, receptor of advanced glycation end products, P-selectin
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