The Relationship Of The Fas,FasL,MMP-9,TIMP-1 And Survivin Gene Variety In The Maternal-fetal Interface With Hypertensive Disorder Complicating Pregnancy

Hypertensive disorder complicating pregnancy is a special disease ingestation, is also the most familiar gestation period complications, threaten thefemale baby's health seriously, The cause of this disease is up to now not clear.Therefore the research that expects hypertensive disorder complicatingpregnancy and the outbreak mechanism to the gestation has been the importanttopic of the obstetrics field. In recent years, along with the foundation medicalscience theories especially molecular biology technical progress, make theresearch of hypertensive disorder complicating pregnancy enter a new ages.Currently the domestic and international scholar will expect the hypertensivedisorder complicating pregnancy research point concentration to the biologycharacteristic and function control of the trophoblastic cell especially in thematernal-fetal interface.The maternal-fetal inerface includes the placenta,the decidual and uterusmuscle layer that the placenta adheres ,which is the direct contact part ofembryo and materal. The placenta trophoblast take the outside embryo layerantigen coming from the embryo, is unique embryo's cell in maternal-fetalinterface connect with maternal immune system directly . The placenta as anatural and of same race and different body transplant, transplanting maternalbody, not rejecting by maternal immune system, explains it to have animportant role in the maternal immunity tolerance. The placenta trophoblastcan also secrete a variety the vascular factor and the cell factor in the meantime,regulating an important function to the normal gestation physiology. Howeverthe placenta trophoblast invade the decidual and the uteral muscle layer tocause spiral small artery of physiology casting-form process.These processesthe are all the adjust by the complications of the various factorses the tocontrol,and it is the thus clear the that the biology characteristic in thematernal-fetal inerface is important to maintain the normal gestation, the thechange of its the biology function may cause the much pathologic gestations,such as recurrent spontaneous abortion , hypertensive disorder complicatingpregnancy and fetal growth restriction ,et al. Therefore many foreign scholarsconcentrates gradually the focus that study to the pathologic gestation on thematernal-fetal interface, hope from it announce to public the direct cause ofdisease of many pathologic gestations in end.Our research choose the matrixmetalloproteinase-9 and tissue inhibitor of metalloproteinase-1, Fas/FasL andthe Survivin gene in the maternal-fetal interface to inquire the relationship withhypertensive disorder complicating pregnancy from the aspect of immune,thetrophoblast invasion and apoptosis and to inquire the outbreak mechanism ofhypertensive disorder complicating pregnancy, providing the theories basis forestablishment theory of hypertensive disorder complicating pregnancy and theclinic treatment.The Fas also calls the CD95 or the Apol -1 belongs to TNF receptorfamily ,it activate and loose gather after combine with its ligant FasL,thenactivate a related death area(FADD) of Fas, the latter activates the Procaspase8formation caspase 8.Caspase 8 start again a series of classes o response andcause apotosis. The Fasl is very limited in the expression part in the body,usually is distribute in immunity to forgive organ (the eye and testicle).All thetrophoblast cells can express Fasl in the whole gestation process, but thegestation expect to be activated T lymphoid cell is a great deal of expressionFas, the Fasl can induce the Fas + T cell apotosis to make the placenta get theimmunity forgive,which is advantageous to an embryo existence.When Fas and Fasl system change, it will make immunity responsestronger in the maternal-fetal interface, but cause hypertensive disordercomplicating pregnancy occurrence.The matrix metalloproteinases (MMPS) is the zinc dependence peptideenzyme that can solute extracellular matrix (ECM).It has an important role inECM metabolism,formation of new blood vessel, the repair of wound and theoccurrence or transference of tumor . The express of MMPs is regulated nicelyin the course of embryo implantation and growth of placenta.,and haveimportant meaning to the occurrence and maintenance of the gestation thenormal gestation.In the course of implantation the trophoblast treacherous actsto invade along the spiral small artery, gradually make the vessel smoothmuscule replaced by fiber protein like material, with the result that the bloodvessel extend,the resistance descend,the blood increases obviously, this kind offollows spiral and small arterial physiology variety drive be called blood vesselto remould. But the trophoblast contrary invasion request it to secrete theeffective hydrolyze to decompound the main composition in the ECM such asvarious collagen, matrix sugar albumen and albumen amylose .The matrixmetalloproteinase is unique valid hydrolyze enmyze ,it secretion decrease willinfluence necessarily the tophoblast invade to the uterine muscle layerandthe blood vessel remould, might cause to have an abortion in earlypregnancy, but in the third trimester might cause to have hypertensive disordercomplicating pregnancy because of placenta implantation superficially.The cell apoptosis is a kind of from the cell independence death method ofthe gene control, calling the procedure cell death ,it act by membrancerecepror and cytoplasm protein. The people's understanding to the apotosisarrives the molecular and the gene level already currently, the cell apotosis hassomething to do with the maintenance of growth of the organization organ andthe normal physiology activity of the machine body, the apotosis also maintainsin the normal pregnancy and the embryo develop aspect to have alreadyemphasized to want a function.The apotosis of excessive or little will cause theoccurrence of the pathologic gestationThe Survivin is a kind of mammal specialrestrain gene of apotisis , expressing scarcely in the normal person organization,but expression in all tumors organizations that is study, providing new target inresearches of the tumor, studying currently of the hot points are concentrated allhere.In maternal-fetal interface the tyophoblast and the decidualto all there arethe Survivin gene and its protein outcome in the meantime, which have animportant regulated function in apotosis.The variety of survivn gene mightcause abnormal apotosis ang pathologic pregnancy. The Survivin gene's researchin the obstetrics realm reports at home and abroad a very few, and there is noreport in the realationship of the abnormality of the Survivin with hypertensivedisorder complicating pregnancy at home and abroad currently.Many foreign scholars currently make the focus of hypertensive disordercomplicating pregnancy research concentrate gradually on the maternal-fetalinterface, hope from it in end announce to public its direct cause of the disease.The domestic is a start to the research of this aspect just, and very not system,also very not thorough.But along with knowledge of maternal-fetal interfacedeepen, the research of that realm will become a hot point in recently years. Atpresent time,the research of MMP and survivin are limited to tumor aspectmainly. The research in MMP-9/TIMP-1,Fas and the Fasl system and itsrelationship with hypertensive disorder complicating pregnancy abroad reportway to be limited by placenta organization only. But the research in thematenal-fetal interface of other parts is no report domestic . The research ofthe Survivin gene, be limited by the tumor aspect more at home and abroad,relate to with hypertensive disorder complicating pregnancy haven't yet seen asimilar research at home and abroad currently.This research through the ELISA method determined soluted Fas level inhypertensive disorder complicating pregnancy and normal third trimesterpregnancy women serum ,using immunohistochemistry method determinedFas/FasL and MMP-9/TIMP-1 expression in maternal-fetal interface,and usingRT-PCR method determined survivin-mRNA level in maternal-fetal interface.To research the relationship of maternal-fetal interface biology characteristicvariety and hypertensive disorder complicating pregnancy from the aspect ofimmune, tophoblast invasion and apotosis .The result show that the maternal serum sFas concentration in mild andsevere pre-eclampsia are higher than in normal third trimester pregnancysignificantly (p<0.05 or p<0.01);the expression of Fas in placenta tophoblastcell are higher in mild and severe pre-eclampsia than in normal third trimesterpregnancy significantly (p<0.05 or p<0.01);but the expression of FasL inplacenta tophoblast cell are lower in mild and severe pre-eclampsia than innormal third trimester pregnancy significantly (p<0.05 or p<0.01);theexpression of Fas in floor decidual cell in severe pre-eclampsia are higher thanin normal third trimester pregnancy(p<0.05);but the expression of FasL infloor decidual cell are lower in mild and severe pre-eclampsia than in normalthird trimester pregnancy significantly (p<0.05 or p<0.01);there are Fasexpression in all grups of uterine muscule at different part , but no different;FasL only express in placenta invasive uterine muscle accidentally,no expressivein uterine muscle at incision .The expression of MMP-9 in placenta tophoblastcell are lower in mild and severe pre-eclampsia than in normal third trimesterpregnancy significantly (p<0.05 or p<0.01), but TIMP-1 expression have nodifferent;the expression of MMP-9 in floor decidual cell in severepre-eclampsia are lower than in normal third trimester pregnancy(p<0.05);theexpression of TIMP-1 in floor decidual cell and placenta invasive muscle arehigher in mild and severe pre-eclampsia than in normal third trimesterpregnancy significantly (p<0.05);there are MMP-9 and TIMP-1 expression inincision muscle ,but no different .In mild and severe pre-eclampsia groups theTIMP-1 expression are higher in placenta invasive muscle than in same groupincision muscle obviously (p<0.05).The survivin-mRNA level in placenta and floor decidual are lower in insevere pre-eclampsia than in normal third trimester pregnancy obviously(p<0.01);but no expression in uterine muscle at different part in all groups.This research shows that the cause of hypertensive disorder complicatingpregnancy has closely relationship with Fas/FasL system mess, MMP-9/TIMP-1unbalance and survivin gene express abnormally.