The Role Of Zinc Gluconate In Antagonizing Oxidative Stress And Angiogenic Imbalance In Preeclampsia-like Rats

Objective: To investigate the role of zinc gluconate in antagonizing the oxidative stress and injury,angiogenic imbalance and the adverse birth outcome in PE model-like rats and to provide a theoretical basis for the possibility of clinical application of zinc gluconate to reduce PE risk by using a PE-like rat model induced with the nitric oxide synthase(NOS)inhibitor Nitro-L-Arginine Methyl Ester(L-NAME)and treated with zinc gluconate in the present study.Methods: Forty pregnant rats were randomly divided into four groups,which were the empty control(lavage and subcutaneous injection of normal saline),the treatment control(lavage of zinc gluconate 5 mg/kg/d and subcutaneous injection of normal saline),the PE model(subcutaneous injection of L-NAME 80 mg/kg/d and lavage of saline),and the PE treatment(lavage of zinc gluconate and subcutaneous injection of L-NAME).Zinc gluconate was administered intragastrically on the day of pregnancy confirmation(P0)in treatment control and PE treatment groups.On the fourth day of pregnancy(P4),L-NAME was subcutaneously injected in PE model and treatment groups.The blood pressure of rats in each group was measured before and after L-NAME treatment.Urine was collected and the urinary protein level was measured.After the animals were sacrificed on P20,the weights of the placenta and the fetuses and the length of the fetal rats were measured to reflect the development of the placenta and fetuses.The biological samples,including blood and placenta,were collected.Determination of superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),metallothionein(MT),malondialdehyde(MDA)and 3-nitrate in serum and placenta homogenate was made to illustrate oxidative stress and injury;Levels of vascular endothelial growth factor(VEGF),placental growth factor(PLGF)and soluble tyrosine kinase-1(s Flt-1)were also analyzed to indicate the angiogenic imbalance.Results: Compared with the empty and treatment controls,the blood pressure and urinary protein levels of the PE model were increased,and the placental weight,fetal rat weight and fetal rat length were significantly decreased.The SOD and CAT activity,GSH,VEGF and PLGF levels decreased,while MDA and 3-NT concentrations increased in serum and placental tissue homogenates.The serum s Flt-1 content increased significantly.After the administration of zinc gluconate,the above parameters are all reversed,approaching or even reaching the levels of the controls.MT levels in serum and placental homogenate of the treatment control and PE treatment groups increased,whereas the MT levels in the PE model were not different from those in the empty control.Conclusion: Subcutaneous injection of L-NAME may cause PE-like rats,whereas zinc gluconate plays a certain role in PE prevention through the antagonization of oxidative stress and injury and the reverse of angiogenic imbalance.