Expression Of Matrix Metalloproteinase-2 And Tissue Inhibitor Of Metalloproteinase-2 In The Placenta Of Pregnancy-induced Hypertension Syndrome Patients

Pregnancy-induced hypertesion syndrome (PIH) is a common complication of pregnancy ,which key character is hypertension , proteinuria and edema . This disorder is still one of the leading causes of maternal and fetal morbidity and mortality . Despite of active research for many years , the etiology and pathogenetic mechanisms of this disorder exclusive to human pregnancy are an enigma . After research ,it is indicated that the low expression of matix metalloproteinases (MMPs) and the unbalanced proportion of MMPs and their inhibitors (TIMPs) are nearly connected with PIH . At present it has been thought that placental ischemia is the starting point of and the obstruction of trophoblastic recoinage is the important tache . During the trophoblastic recoinage , the hydrolyzing of matix and the traversing of a series of basement membranes including endometrial epithelium and gland , blood vessel , decidua and so on is the key . The major ingredients of basement membrane include type IV collagenase , LN, fibrin and so on , which are the mostly acted object of MMP-2 and MMP-9 . It is indicated that MMP-2 and MMP-9 play a chiefly role on the trophoblast recoinage . During the embryogeny , the genes of MMPs are activated and trophoblasts secrete and express plenty of MMP-1, MMP-2 and MMP-9 , which are showed that MMPs play a vital role in trophoblast invasion . Objective Through studying the expression of MMP-2 and TIMP-2 in the placenta of the women with normal pregnancy and PIH , we probe into the relationship of incidence mechanism of PIH and them . It will make us more understand pathogeny of PIH and will inaugurate a new way for the preventing and diagnosis-therapy of PIH . Method The placenta tissues are from the women with delivery in the NO.2 hospital of jilin university and genecology and obstetics hospital of changchun from Dec. 2003 to Sep. 2004 . The total number is 64 , and 15 of it is from the women with normal pregnancy (control team) and 49 of it is from the women with PIH (experimentation team) . The number of low-grade , middle-grade ,severe-grade PIH team are respective 12, 17 ,20 . The age , pregnant weeks and delivery times of the women in two teams are all not significant difference (p>0.05)and they all have not the ill history of primary hypertesion , diabetes chronic nephritis and so on . The diagnostic standard of PIH refers to the NO.5 edition <> compiled by lejie . After the delivery of pregnant women , we collect placenta tissues immediately and fix them by 10% formalin and embed them by paraffin 。We perform an immunohistochemical method to detect the positive expression ratio of MMP-2 and TIMP-2 in the placenta of the women with normal pregnancy and PIH and analyse the data by statistical software . Result 1.The positive expression of MMP-2 and TIMP-2 is in the plasma of trophoblast , deciduas cell , mesenchyme cell , vascular endothelial cell of the placentas of women with normal pregnancy , which it is mostly middle-grade and high-grade , and MMP-2 and TIMP-2 distribute diffusely . But the positive expression of MMP-2 is not in mesenchyme cell and vascular endothelial cell of the placentas of women with PIH . The expression of MMP-2 is mostly weak positive in PIH . The positive expression of MMP-2 has significant difference in PIH contrasting with normal pregnancy team (P<0.05). While that of TIMP-2 has not significant difference(P>0.05). The positive expression ratio of MMP-2 in trophoblast is higher and the positive expression ratio of TIMP-2 in deciduas cell is higher in the placentas of women with both normal pregnancy and PIH . 2. The positive expression of both MMP-2 and TIMP-2 has notsignificant difference in low-grade , middle-grade ,severe-grade PIH team(P>0.05). The expression of TIMP-2 is not in mesenchyme cell of middle-grade PIH and in mesenchyme cell and vascular endothelial cell of severe-grade PIH . With the aggravation of state of an illness , the positve expression of MMP-2 and TIMP-2 in PIH is reduced gradually , and the former is more significant . 3.The positive expression ratio of MMP-2 and TIMP-2 in PIH is significantly lower than normal pregnancy team , and with the aggravation of state of an illness , the positve expression ratio in PIH is reduced gradually . Discussion The study shows that the expression of MMP-2 in the placentas of PIH is significantly reduced , while the difference of the expression of TIMP-2 is not significant . So the ratio of MMP-2 and TIMP-2 in PIH is significantly reduced . It embodies the fall of trophoblast soakage ability . It also tells us that as MMP-2 secreted and expressed by trophoblast is reduced and the ratio of MMP-2 and TIMP-2 is significantly reduced , which restricts trophoblast soakage ability , it causes villus to develop badly and small helix artery to recoin incapably . The reason of the fall of MMP-2 in PIH is an enigma . But , in gestation both trophoblast and deciduas cell can synthesize and secrete kinds of cell factors and these factors can adjust trophoblast to synthesize and secrete MMPs by way of selfsecreting or sidesecreting . The most of cell factors of promoting trophoblast to proliferate and move can accelerate the synthesis and secreting of MMPs and inversely MMPs can accelerate the release of these factors in matrix after analyzing matrix . Both those cell factors and MMPs promote trophoblast to erode . Some studies show that the expression of insulin-like growth factor-II(IGF-II) , hepatocyte growth factor(HGF) and vascular endothelial growth factor(VEGF) in the placenta of PIH are all reduced . The low level of MMPs may be correlated with the fall of those factors . In addition , the...