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

Part Ⅰ A clinical research about the kidney injury of preeclampsiaObjective:To explore the relationship between the severity of kidney injury in preeclampsia and the pregnancy outcomes.Methods:The clinical materials of153preeclampsia patients admitted to the Obstetrics and Gynecology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between January2009and December2011were analysed retrospectively. The preeclampsia patients were divided into3groups A, B and C according to the proteinuria results (+),(2+) and (3+). The patients of each group were57,35and61respectively. The blood pressure, album content in serum, renal function and the index involved in outcomes of neonatal of the3groups were compared.Result:The contents of urea, creatinine and uric acid, blood pressure and ultrasound S/D of group C were significantly increased compared with other two groups. The more proteinuria was detected, the higher consistency of serum urea, creatinine and uric acid was observed. The album of serum was significantly decreased in group C compared with othertwo groups, the termination time was earlier, the weight of placenta and neonatal was lightened (p<0.05). The mortality rate of neonatal was increased and the amniotic fluid pollution was serious.Conclusion:The content of the proteinuria in preeclampsia is associated with the severity 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 on human glomerular endothelial cells injuryObjective:To investigate the effects of preeclampsia serum on the injury of the human glomerular endothelial cells, in order to study the mechanism of proteinuria formation in preeclampsia.Methods:The normal pregnancy and preeclampsia serum was collected, each group was12cases. 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 the barrier function of human glomerular endothelial cells monolayer;2. Fluorescent quantitation PCR was used to test the expression of ET-1;3. CCK8was used to detect the proliferation ability of the human glomerular endothelial cells and4. The apoptosis detection kit was used to detect the apoptosis rate of the human glomerular endothelial cells.Result:Compared with FBS group1. The transfer of fluorescently-labeled BSA across the human glomerular endothelial cells monolayer was much higher in the preeclampsia group;2. The ET-1mRNA expression of the human glomerular endothelial cells was significantly increased in preeclampsia group;3. The indexes in the normal pregnancy group showed no significant difference compared with the FBS group. The proliferation ability and apoptosis rate were detected no difference among all the groups.Conclusion:Preeclampsia serum might cause injury to glomerular endothelial cells and destroy the barrier function of glomerular endothelial cell. The increase of glomerular endothelial cell permeability might be the mechanism of the formation of proteinurian in preeclampsia. Part Ⅲ The effect of low molecular weight heparin on the injury of human glomerular endothelial cells through antagonizing exogenous heparanase ⅢObjective:1. To investigate the protective effects of low molecular weight heparin on the human glomerular endothelial cells interfered with preeclampsia serum;2. To study the role of low molecular weight heparin in protective mechanism of the human glomerular endothelial cells permeability dysfunction through antagonizing exogenous heparanase Ⅲ.Methods:1. Low molecular weight heparin was added into the medium of human glomerular endothelial cells interfered with preeclampsia serum. Transwell and FITC-BSA were 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 detective indexes were compared with the preeclampsia group, in order to evaluate the injury of the human glomerular endothelial cells.2. The FBS, exogenous heparanase Ⅲ and exogenous heparanase Ⅲ plus low molecular weight heparin were added into the medium of human glomerular endothelial cells. Transwell and FITC-BSA were used to detect the barrier function of human glomerular endothelial cells monolayer. The differences of human glomerular endothelial cells 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 low molecular weight heparin group, which meant the barrier function of the human glomerular endothelial cells monolayer was improved. The ET-1mRNA expression of the human glomerular endothelial cells was significantly decreased. The proliferation ability and apoptosis rate showed no difference.2. The transfer of fluorescently-labeled BSA across the human glomerular endothelial cells monolayer in the exogenous heparanase Ⅲ group was much higher than in the FBS group. However, the transfer was significantly lower when low molecular weight heparin was added, and showed no difference compared with the FBS group.Conclusion:Low molecular weight heparin could alleviate the human glomerular endothelial cells injury caused by the preeclampsia serum, and antagonize the devastating effect of exogenous heparanase Ⅲ on the permeability of human glomerular endothelial cells. Low molecular weight heparin might protect the barrier function of glomerular endothelium by antagonizing heparanase, so as to reduce the formation of proteinuria in preeclampsia.