The Effect Of Low Molecular Weight Heparin On Glomerular Endothelium Injury Of Pre-eclampsia Through Antagonizing Heparanase

Part Ⅰ A clinical research about the kidney injury of preeclampsiaObjective: To explore the relationship between the severity of kidney injury inpreeclampsia and the pregnancy outcomes.Methods: The clinical materials of153preeclampsia patients admitted to theObstetrics and Gynecology of Tongji Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology between January2009and December2011wereanalysed retrospectively. The preeclampsia patients were divided into3groups A, B and Caccording to the proteinuria results (+),(2+) and (3+). The patients of each group were57,35and61respectively. The blood pressure, album content in serum, renal function and theindex involved in outcomes of neonatal of the3groups were compared.Result: The contents of urea, creatinine and uric acid, blood pressure and ultrasoundS/D of group C were significantly increased compared with other two groups. The moreproteinuria was detected, the higher consistency of serum urea, creatinine and uric acid wasobserved. The album of serum was significantly decreased in group C compared withothertwo groups, the termination time was earlier, the weight of placenta and neonatal waslightened (p<0.05). The mortality rate of neonatal was increased and the amniotic fluidpollution was serious.Conclusion: The content of the proteinuria in preeclampsia is associated with theseverity of kidney injury, the patients’ condition and the outcomes of neonatal. The content of proteinuria could imply the severity of preeclamptic patients’ condition. Part Ⅱ The effect of normal pregnancy and preeclampsia serum onhuman glomerular endothelial cells injuryObjective: To investigate the effects of preeclampsia serum on the injury of thehuman glomerular endothelial cells, in order to study the mechanism of proteinuriaformation in preeclampsia.Methods: The normal pregnancy and preeclampsia serum was collected, each groupwas12cases. The serum was added into the medium of human glomerular endothelial cells,FBS was taken as comparison and1. Transwell and FITC-BSA were used to detect thebarrier function of human glomerular endothelial cells monolayer;2. Fluorescentquantitation PCR was used to test the expression of ET-1;3. CCK8was used to detect theproliferation ability of the human glomerular endothelial cells and4. The apoptosisdetection kit was used to detect the apoptosis rate of the human glomerular endothelialcells.Result: Compared with FBS group1. The transfer of fluorescently-labeled BSAacross the human glomerular endothelial cells monolayer was much higher in thepreeclampsia group;2. The ET-1mRNA expression of the human glomerular endothelialcells was significantly increased in preeclampsia group;3. The indexes in the normalpregnancy group showed no significant difference compared with the FBS group. Theproliferation ability and apoptosis rate were detected no difference among all the groups.Conclusion: Preeclampsia serum might cause injury to glomerular endothelial cellsand destroy the barrier function of glomerular endothelial cell. The increase of glomerular endothelial cell permeability might be the mechanism of the formation of proteinurian inpreeclampsia. Part Ⅲ The effect of low molecular weight heparin on the injury ofhuman glomerular endothelial cells through antagonizingexogenous heparanase ⅢObjective:1. To investigate the protective effects of low molecular weight heparin onthe human glomerular endothelial cells interfered with preeclampsia serum;2. To study therole of low molecular weight heparin in protective mechanism of the human glomerularendothelial cells permeability dysfunction through antagonizing exogenous heparanase Ⅲ.Methods:1. Low molecular weight heparin was added into the medium of humanglomerular endothelial cells interfered with preeclampsia serum. Transwell and FITC-BSAwere used to detect the barrier function of human glomerular endothelial cells monolayer.Fluorescent quantitation PCR was used to test the expression of ET-1. The detectiveindexes were compared with the preeclampsia group, in order to evaluate the injury of thehuman glomerular endothelial cells.2. The FBS, exogenous heparanase Ⅲ and exogenous heparanase Ⅲ plus lowmolecular weight heparin were added into the medium of human glomerular endothelialcells. Transwell and FITC-BSA were used to detect the barrier function of humanglomerular endothelial cells monolayer. The differences of human glomerular endothelialcells permeability among the groups were compared.Result:1. Compared with preeclampsia group, the transfer of fluorescently-labeled BSA across the human glomerular endothelial cells monolayer was much lower in the lowmolecular weight heparin group, which meant the barrier function of the human glomerularendothelial cells monolayer was improved. The ET-1mRNA expression of the humanglomerular endothelial cells was significantly decreased. The proliferation ability andapoptosis rate showed no difference.2. The transfer of fluorescently-labeled BSA across the human glomerular endothelialcells monolayer in the exogenous heparanase Ⅲ group was much higher than in the FBSgroup. However, the transfer was significantly lower when low molecular weight heparinwas added, and showed no difference compared with the FBS group.Conclusion: Low molecular weight heparin could alleviate the human glomerularendothelial cells injury caused by the preeclampsia serum, and antagonize the devastatingeffect of exogenous heparanase Ⅲ on the permeability of human glomerular endothelialcells. Low molecular weight heparin might protect the barrier function of glomerularendothelium by antagonizing heparanase, so as to reduce the formation of proteinuria inpreeclampsia.