Study On The Role Of MMP-9, TIMP-1and TGF-β1in Hypertensive Disorders In Pregnancy

Objective: Hypertensive disorders in pregnancy is a specific illness inpregnancy, it is the most important cause resulting in morbidity and mortalityin mothers and neonates.The conclusive etiology of hypertensive disorders inpregnancy remains unclear now. The scholars put forward the theories ofimmunity mechanism, the placenta or trophocyte ischemia, oxidative stressand heredity. In recent years, it is generally believed that the theory ofplacenta or trophocyte cells ischemia is the key of pathogenesis. Placentalischemia is the cause of the physical vascularremoulding of spiral arterial,which might result in defective nidation. Martix metalloproteinases-9(MMP-9)is particularly important in the processes of cytotrophoblastinvasion, the spiral arterial rebuilding and the placenta formation, which candegrade extracellular matrix efficiently. Tissue inhibitor of metalloproteinase-1(TIMP-1) is the specific inhibitors of MMP-9, which combined with MMP-9can effectively adjust its formation and biological activity. They can controlthe invasion of cytotrophoblasts together. Transforming growth factor beta1(TGF-β1) was discovered in1981as a multifunctional growth factor, on cellgrowth differentiation, extracellular matrix formation, inflammation, thebody’s immune, interstitial fibrosis and the formation of tumor blood vesselsand so on various aspects has a wide range of adjustment. Through studyingthe role of MMP-9、 TIMP-1and TGF-β1in the placenta of hypertensivedisorders in pregnancy, we want to provide the evidence of experimenttheories for clinical precaution and treatment.Methods:190cases of obstetric patients(30cases with light preeclampsia，30caseswith severe preeclampsia,30cases with normal pregnancy)who excepted otherdisease were recruited the fourth affiliated hospital of HeBei medical university from December2011to March2013.About1cm×1cm×1cmplacental tissues were gathered from the pregnant women after the placentawas deliveried in30minutes. Then we fix them in10%formalin24-48h andembed them in paraffin. Chip them continuous in the size4μm thick.2The expression of MMP-9,TIMP-1,TGF-β1in placenta was researchedby the method of immunohistochemical SP.3All the data was processed by the Excel and analyzed by SPSS13.0software wrap, Kruskal-wallis H Test, Wilcoxon signed-rank test, Fisherprobabilities in2×2table and Spearman grade relation analysis are involved.Statistically significant level was considered a“salpha equals0.05”“,P≤0.05”indicating significant difference,“P≤0.01” indicating very significantdifference.Results:1There were no statistical difference between control and study group in ageand gestational weeks (P>0.05).2The expression of MMP-92.1Immunohistochemical staining for MMP-9was located at the cytoplasmand membrane of the cytotrophoblast as well as extra villous trophoblasticcells, some signals were showed in the cytoplasm of the vascular endotheliumdecidualcell、 hemal endothelial cells and mediate cells. The expression ofMMP-9in trophocyte showed significant lower in light preeclampsia groupand severe preeclampsia group (positive rate=70.00%&36.67%) than incontrol group (positive rate=96.67%)(P=0.014<0.05, P=0.001<0.05).2.2The expression of MMP-9is different from control group to lightpreeclampsia group and severe preeclampsia group, the significance isstatisticlly(P=0.002<0.05).The expression in light preeclampsia group and insevere preeclampsia group are lower than that in control group (P=0.013<0.05,P=0.008<0.05).The expression in severe preeclampsia group is lower than thatin light preeclampsia group (P=0.015<0.05).The expression of MMP-9haddecreasing tendency follow up the severity degree of patient’s condition. 3.1TIMP-1was expressed in the cytoplasm and membrane of thecytotrophoblast as well as extra villous trophoblastic cells, some signals wereshowed in the cytoplasm of the vascular endothelium decidualcell、 hemalendothelial cells and mediate cells. The expression of TIMP-1in trophocyteshowed significant higher in light preeclampsia group (positive rate=73.33%)than in control group (positive rate=40.00%)(P=0.011<0.05). The expressionof TIMP-1in trophocyte showed significant higher in severe preeclampsiagroup (positive rate=90.00%) than in control group (P=0.005<0.05).3.2The expression of TIMP-1is different from control group to lightpreeclampsia group and severe preeclampsia group, there is statisticsignificance (P=0.004<0.05).The expression in light preeclampsia group ishigher than that in control group (P=0.024<0.05). The expression in severepreeclampsia group is higher than that in control group (P=0.018<0.05).Theexpression in severe preeclampsia group is higher than that in lightpreeclampsia group (P=0.027<0.05).The expression of TIMP-1had increasingtendency follow up the severity degree of patient’s condition.4The expression of TGF-β14.1TGF-β1was expressed in the cytoplasm and membrane of thecytotrophoblast as well as extra villous trophoblastic cells and mediate cells,some weak signals were showed in the cytoplasm of the vascular endotheliumdecidualcell and hemal endothelial cells. The expression of TGF-β1introphocyte showed significant higher in light preeclampsia group (positiverate=76.67%) than in control group(positive rate=33.33%)(P=0.010<0.05).The expression of TGF-β1in trophocyte showed significant higher in severepreeclampsia group (positive rate=93.33%) than in control group (P=0.002<0.05).4.2The expression of TGF-β1is different from control group to lightpreeclampsia group and severe preeclampsia group, there is statisticsignificance (P=0.001<0.05).The expression in light preeclampsia group ishigher than that in control group (P=0.022<0.05). The expression in severepreeclampsia group is higher than that in control group(P=0.014<0.05).The expression in severe preeclampsia group is higher than that in lightpreeclampsia group(P=0.036<0.05).The expression of TGF-β1hadincreasing tendency follow up the severity degree of patient’s condition.5MMP-9was negative correlate to TIMP-1and TGF-β1in placenta. TIMP-1was positive correlate to TGF-β1in placenta.Conclusion:1There are different expressions of MMP-9, TIMP-1and TGF-β1incontrol group, light preeclampsia group and severe preeclampsia group.2MMP-9was negative correlate to TIMP-1and TGF-β1in placenta.TIMP-1was positive correlate to TGF-β1in placenta.The expression ofMMP-9placenta had decreasing tendency follow up the severity degree ofhypertensive disorders in pregnancy, and the expression of TIMP-1andTGF-β1located in placental syncytiotrophoblast had increasing tendencyfollow up the severity degree of condition.3High expression of TGF-β1in placenta of the patients withhypertensive disorders in pregnancy affect the erosion of trophoblastic cells,make TIMP-1express highly and then make MMP-9express lowly.Insufficient trophoblasts infiltration influences the physical vascular-remoulding of spiral arterial and might result in defective nidation. Thesechanges lead to the pothogenesy of hypertensive disorders in pregnancy.Wewill get the accurate mechanism of hypertensive disorders in pregnancy byfurther research in the molecular biology level, which will provide theoriesevidence of earlier period prevention and treatment.