The Experimental On The Relationship Between Trophoblastic Autophagy And The Pathogenesis Of Preeclampsia

Objective:The purpose of this study is to investigate whether the expression of vascular endothelial growth factor(VEGFA),soluble fms-like tyrosine kinase-1(sFLT1)and apoptosis related genes(Bcl-2 and Bax)was regulated by autophagy and to determine the relationship between trophablsts autophagy and preeclampsia.Methods:1.Human placental tissues were collected from normotensive pregnancies(CON,N=10)and early-onset preeclampsia pregnancies(EOPE,N=10)in women who underwent caesarean delivery;Transmission electron microscopy was applied to identify the autophagolysosomes;Then we detected the placental levels of LC3,Beclin-1,VEGFA,sFLT1,Bcl-2 and Bax in preeclampsia and normal women;2.In vivo experiment:We evaluated the expression of superoxide dismutase(SOD),LC3,Beclin-1,VEGFA,sFLT1,Bcl-2,Bax and the migration ability of human trophoblast HTR8/SVneo cells which were exposed to oxidized low-density lipoprotein(ox-LDL)1%O2,Rapamicin or Chloroquine.Results:1.The number of autophagolysosomes was reduced in EOPE group compared with control group,the mRNA and protein expression of LC3 and Beclinl were decreased,the mRNA expression of VEGFA and Bcl-2 were decreased,the mRNA expression of sFLTl and Bax were increased;2.The mRNA expression of VEGFA,Bcl-2 and SOD were decreased,the mRNA expression of sFLTl and Bax were increased when the human trophoblast HTR8/SVneo cells was treated with ox-LDL;The migration ability of human trophoblast HTR8/SVneo cells was decreased and apoptosis ratio under ox-LDL treatment was increased;3.The mRNA expression of VEGFA and SOD was upregulated,the mRNA expression of sFLTl and Bax were downregulated,migration ability was increased and apoptosis ratio was decreased when autophagy activated in HTR8/SVneo cells;After the inhibiton of autophagy,the results were contrary.Conclusions:1.VEGFA downregulated,sFLTl and Bax upregulated may associated with autophagy impairation in EOPE;2.Ox-LDL is capable of mimicking the microenvironment of preeclampsia dysfunction,suppressing angiogenesis by regulating the expression of VEGFA and sFLTl and increasing apoptosis of HTR8/SVneo cells,and autophagy activation could play a protective role in these reactions.