The Effect Of AGEs-RAGE System In Rats With Gestational Diabetes Mellitus On Placental Vascular Permeability

Objective To study the alteration of placental vascular permeability and AGEs-RAGE system in GDM rats and whether the alteration of placental vascular permeability is related to the alteration of AGEs-RAGE system by LMWH intervention.Methods 1)60 female SD rats(250-300 g)and 30 adult male SD rats(300-350 g)were allowed to mate(2:1 caged),and the female rats that were found sperm in their vaginal smear were considered pregnant for fisrt day.Adult pregnant rats were randomly divided into three groups:GDM group,NC group,and LMWH group.2)Rats in GDM group and LMWH group were administered streptozotocin(STZ)intraperitoneally to induce GDM rats model,and rats in NC group received equal citrate buffer.Three days later,random blood glucose over 16.7 mmol/L was a success.3)Rats in LMWH group received LMWH(600IU/kg)subcutaneously since pregnant day 5.4)All rats were sacrificed through cervical dislocation at pregnant day 16 and placenta was removed by cesarean section.The vascular permeability was measured by Miles assay presented by leakage of Evans Blue.Maternal serum levels of AGEs were measured by AGE ELISA kit.RT-PCR was adopted to measure the expression of VEGF mRNA and RAGE mRNA.Endothelial cell tight junction protein Occludin was detected by western blot.Results 1)GDM rats exhibited a significant increase in leakage of Evans Blue,serum levels of AGEs and expression of VEGF mRNA and RAGE mRNA when compared with the control rats(leakage of Evans Blue,0.53±0.05ng/mg vs 0.35±0.06ng/mg,P<0.01;serum levels of AGEs,121.26±28.22ng/ml vs 67.43±22.84ng/ml,P<0.01;expression of VEGF mRNA,P<0.01;expression of RAGE mRNA,P<0.01).The expression of Occludin was reduced in GDM rats(P<0.05)compared to control rats.2)The intervention of LMWH resulted in a significant decrease in leakage of Evans Blue and expression of VEGF mRNA when compared with GDM rats(leakage of Evans Blue,0.44±0.02ng/mg vs 0.53±0.05ng/mg,P<0.05;expression of VEGF mRNA,P<0.01).The expression of Occludin was higher in rats treated with LMWH than that in GDM group(P<0.05).There were no differences between LMWH group and GDM group in serum levels of AGEs and expression of RAGE mRNA.Conclusions 1)There is an increase in placental vascular permeability and expression of AGEs-RAGE system in GDM rats.The alteration of placental vessel may be associated with the alteration of AGEs-RAGE system.2)The intervention of LMWH exhibits a protective effect against GDM in alteration of vascular permeability.This result will be helpful for the therapy of gestational diabetes mellitus in future.