Effect Of S100 Calcium Binding Protein A12 On The Pathogenesis Of Preeclampsia

ObjectivePreeclampsia is a common and obstetrics severe disease in hypertensive disorders in pregnancy, is the second leading cause of maternal death in our country, which is a systemic disease and affects the maternal and infant health, therefore it is the main reason of maternal and perinatal death. Preeclampsia pathogenesis is still unclear, its incidence is as high as 7% to 12%. According to a lot of studies, the inflammation and vascular endothelial injury mechanism of preeclampsia has been attented again. More and more scholars realized that preeclampsia is a matrix of pregnacy to an excessive inflammation. The vascular endothelial injury is part of intravascular excessive sexual inflammation.S100A12 is a member of the calcium binding protein, is a kind of proinflammatory media discoered in recent years.To participate in immune defdese and inflammation, regulating the cell growth-differentiation, inhibition, and apoptosis. S100A12 has unique structure and function that make vascular endothelial adhesion molecule to raise, activation of inflammatory cells, chmical chemotaxis and antimicrobial. S100A12 has also binding the RAGE to activate intracellular signal pathways, which produced a serise of pathological damage, to participate in the process of pathogenesis in atherosclerosis, arthritis and so on.At present,it is unclear whether S100A12 relations with preeclampsia.To detect the expression of S100A12 in materal periphera blood, placenta of preeclampsia, and investigate the effects of plasma from the patients with preeclampsia on proliferation, apoptosis of trophoblast cell, invasive ability and the expression of RAGE, and to explore the significance of S100A12 in preeclampsia. Methods1. First Affiliated Hospital of Zhengzhou University, a total of 60 women with preeclampsia(including 30 cases of mild preeclampsia, 30 cases of severe preeclampsia) was a study group and 30 normal pregnant women was a control group.2. The levels of S100A12 protein in maternal peripheral blood were detected by ELISA. Immunohistochemistry of biotin streptomyces protein peroxidase(SP) method was used to measure the protein expression level of S100A12. The Trophoblast cells were cultured in vitro with plasma from the three groups.and a blank control group was set up as well.Proliferation and apoptosis of trophoblast cell were measured by MTT assay and flow cytometry.Transwell detected the cytotrophoblast invasion ability.Western blot was used to measure the protein expressionlevel of RAGE.3. Using SPSS 17.0 software for the statistic analysis of data. Results is expected to be shown by x ±s, one-way ANOA or chi-square test for the pairwise comparisons in groups. In addition, LSD- test is used for pairwise comparisons, and the correlation of two variables uses Spearman correlation analysis in this study. The inspection level, α=0.05。 Results1. The expression of S100A12 protein in the three groups were as following: mild group:( 30.75±2.68) μg/L、seveer group:( 49.26±4.13) μg/L、control group(15.83±1.42) μg/L. The level of S100A12 in maternal peripheral blood in the mild and severe preeclampsia groups were significantly higher than it in the healthy implantation;3. The serum of preeclampsia induced RAGE high expression in cytotrophoblast, it suggested that the high expression of S100A12 and receptor RAGE may have some effect on the pathogenesis of preeclampsia. pregnant women group(P<0.05).2. The expression positive rates of S100A12 protein in the three groups were as following: mild preeclampisa group76%; severe preeclampsia group93%; healthy pregnant women group23%. The positive rates of placenta in the mild and severe preeclampsia groups were significantly higher than it in the healthy pregnant women group(P<0.05).3.The proliferation rate of trophoblast cell in the mild and severe preeclampsia groups[(77.3±2.1)% and(51.8±2.3) % ]were significantly lower than that in the healthy pregnant women group and the control group[(85.2±2.9) %and(100.0±0.0)%,P<0.05].4.The early apoptosis rate,middle-late apoptosis rate and total apoptosis rate of trophoblast cell in the mild and severe preeclampsia groups[total apoptosis rate were(36.62±1.97)%and(49.29±2.00)%]were significantly higher than those in the healthy pregnant women group and the control group[total apoptosis rate were(18.04±1.89)%and(6.16±1.83)%,P<0.05].5.Cytotrophoblast invasion ability in the mild and severe preeclampsia groups[(29.1±3.2)and(16.8±2.5)]were significantly lower than that in the healthy pregnant women group and the control group[(38.6±24.3)and(42.6±5.6),P<0.05].(4)The expression of RAGE protein in the four groups were as following: mild preeclampisa group(0.479±0.038); severe preeclampsia group(0.651±0.058); healthy group(0.327±0.024); the control group(0.194±0.011). The expression of RAGE protein in the mild and severe preeclampsia groups were significantly higher than those in the healthy and the control group(P<0.05). Conclusions1. The expression of S100A12 increased in materal peripheral blood and placenta, it prompts S100A12 may play an important role in the pathogensis of preeclamsia;2. The serum of preeclampsia can inhibit proliferation, promote apoptosis and reduce the invasive ability, it suggested that the serum may cause shallow placenta implantation;3.The serum of preeclampsia induced RAGE high expression in cytotrophoblast it suggested that the high expression of S100A 12 and receptor RAGE may have some effect on the pathogenesis of proeeclampsia.