Research Of Protective Effect Of BFGF On Vascular Endothelial Cell Damage In Preeclampsia

ObjectivesTo investigate the concentrations changes of soluble Intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhension-1(sVCAM-1)and basic fibroblast growth factor(bFGF) in serum of patients with preeclampsia and the activition of nuclear factor-kappaB(NF-KB) and expression of ICAM-1,VCAM-1 in the vascular endothelial cell line (ECV-304) stimulated by serum from patients with preeclampsia, determine their relationship with endothelial damage and whether bFGF have protective effect on vascular endothelial cell damage stimulated by serum from patients with preeclampsia.Methods1.The serum concentrations changes of sICAM-1, sVCAM-1 and bFGF and their relationship with endothelial damage in patients with preeclampsia.30 patients with preeclampsia(PE group: 15 mild PE, 15 severe PE) and 10 women with normal pregnancy(NP group) were recruited as case group and control group, respectively. there were not significant defferent in age and gestational age. Enzyme-linked immunosorbent assay was used to measure serum concentrations of sICAM-1, sVCAM-1 and bFGF. Results were analyzed by T test and Bivariate correlation. P＜0.05 was considered statistically significant.2. The effect of severe preeclampsia sera on ECV-30415 patients with severe preeclampsia(PE group) and 10 women with normal pregnancy (NP group)were recruited as case group and control group, respectively. there were not significant defferent in age and gestational age. ECV-304 were incubated with 20% serum from severe preeclamptic patients and normal pregnant women for 24 hours. Immunocytochemical staining, Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed to detect the relative content of ICAM-1, VCAM-1 mRNA and ICAM-1, VCAM-1 and NF-κB protein in cells. Results were analyzed by T test and Bivariate correlation. P＜0.05 was considered statistically significant.3.The protective effect of bFGF on ECV-304 stimulated by serum from severe preeclampsia15 patients with severe preeclampsia (PE group) and 10 women with normal pregnancy(NP group) were recruited as case group and control group, respectively. there were not significant defferent in age and gestational age. ECV-304 were incubated with 20% serum from severe preeclamptic patients and 10ng/ml bFGF (PE+bFGF10 group) for 24 hours. Immunocytochemical staining, Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed to detect the relative content of ICAM-1, VCAM-1 mRNA and ICAM-1, VCAM-1 and NF-κB protein in cells. Results were analyzed by T test and Bivariate correlation. P＜0.05 was considered statistically significant.Results1.The serum concentrations changes of sICAM-1, sVCAM-1 and bFGF and their relationship with endothelial damage in patients with preeclampsia.(1) Serum sICAM-1 and sVCAM-1 concentrstions were significantly higher in mild and severe PE group than that in NP group. Serum sICAM-1 and sVCAM-1 concentrstions were significantly higher in severe PE group than that in mild PE group.(2) Serum bFGF level was significantly higher in PE'group than that in NP group. Serum bFGF level was significantly higher in mild PE group than those in NP and severe PE group.(3) Negative correlation between serum bFGF level and sICAM-1 and sVCAM-1 concentrstions was found significantly in PE group.2. The effect of severe preeclampsia sera on ECV-304(1) The percentage of ECV304 which showed staining for ICAM-1,VCAM-1and NF-κB was significantly greater for PE group as compared to NP group.(2) ECV-304 in PE group expressed more ICAM-1 and VCAM-1 mRNA and ICAM-1, VCAM-1 and NF-κB protein than that in NP group.(3) Positive correlation between Activation of endothelial NF-κB and expression of ICAM-1, VCAM-1 mRNA and protein was found significantly in PE group.3. The protective effect of bFGF on ECV-304 stimulated by serum from severe preeclampsia(1) The percentage of ECV-304 which showed staining for ICAM-1,VCAM-1 and NF-κB was significantly less for PE+bFGF10 group as compared to PE group. The percentage of ECV-304 which showed staining for NF-κB in PE+bFGF10 group was significantly greater than that in NP group.(2) ECV-304 in PE+bFGF10 group expressed less ICAM-1 and VCAM-1 mRNA and ICAM-1, VCAM-1 and NF-κB protein than that in PE group and expressed greater ICAM-1 and VCAM-1 mRNA and ICAM-1, VCAM-1 and NF-κB protein than that in NP group.(3) Positive correlation between inhibit level of endothelial NF-κB activation and expression of ICAM-1,VCAM-1 mRNA and protein was found significantly in PE+bFGFlO group.Conclusion1. Serum bFGF level was higher in mild PE group and lower in sever PE group, there had significantly negative correlation between serum bFGF level and sICAM-1 and sVCAM-1 concentrations, Indicating bFGF may act as protective factor for endothelial cells in serum.2. Endothelial NF-κB is activated by Sera from severe preeclamptic patients and led to significant up-regulation of endothelial ICAM-1 and VCAM-1 expression. They are all involved in the pathophysiology of preeclampsia.3. Extrinsic source bFGF inhibit endothelial NF-κB activation significantly which are stimulated by serum from severe preeclamptic patients and result in a significant decrease of endothelial ICAM-1 and VCAM-1 expression, indicating an important role for bFGF in protecting endothelial cells from damage, which provide an evidence to treat preeclampsia using extrinsic source bFGF or inhibitor of NF-κB.