Research On The Expression Of HMGB1/TLR4and NF-κB Signaling Pathway In The Preeclampsia

Objective:1.To evaluate the expression and discussion on high mobility group protein(HMGB1)/toll like receptor4(TLR4) and NF-κB possible role in the signalingpathway in preeclampsia.2To evaluate the correlations between the expression of placenta and serum HMGB1,TLR4and NF-κBp65in PE.Methods: To select10cases of patients with mild preeclampsia,20patients withsevere preeclampsia and30cases of normal pregnancy as a research object in thesame period.1.to navigate the qualitative expression of the HMGB1,TLR4,NF-κBp65protein inplacenta tissue using Immunohistochemical staining.2.Reverse transcription-polymerase chain reaction (RT-PCR) were performed todetect mRNA for HMGB1,TLR4and NF-ΚB p65.3.Levels of HMGB1,TLR4,NF-κBp65in blood serum were measured by ELISA.Results:1.There were no statistical difference between preeclampsia and control group inmateral age (p>0.05);But women with preeclampsia were higher than control groupin MAP,systolic blood pressure, diastolic blood pressure, newborn weight(p＜0.05);Pregnant women with severe preeclampsia group had the earlier termination ofpregnancy than the control group (p＜0.05),there were no statistical differencebetween mild preeclampsia group and control group at the time of termination ofpregnancy (p>0.05).2.1Immunohistochemistry showed that the expression of HMGB1group of normalpregnancy were mainly located in placental syncytiotrophoblasts,in vascularendothelial cells and a few in the stromal cells of cell nucleus. HMGB1in the mildpreeclampsia group and severe preeclampsia group placenta were mainly located in placental syncytiotrophoblasts、in vascular endothelial cells and a few in the stromal cells of cellnucleus and cytoplasmic. Both TLR4and NF-κBp65were mainly located in placentalsyncytiotrophoblasts、in vascular endothelial cells and a few in the stromal of cellsmembrane and cytoplasmic；2.2Immunohistochemistry showed that the expression of HMGB1,TLR4,NF-Bp65were stronger than that of control group in the placental of preeclampsia（P＜0.0125);But HMGB1,TLR4,NF-κBp65in placenta of patients with severepreeclampsia and mild preeclampsia comparison of the differences is no statisticallysignificant（P＞0.0125).3.1RT-PCR showed that both the expression of HMGB1mRNA,TLR4mRNA andNF-κBp65mRNA in the placenta of PE were stronger than that of control group（P＜0.05); But HMGB1mRNA,TLR4mRNA,NF-κBp65mRNA in placenta of patientswith severe preeclampsia and mild preeclampsia comparison of the differences is nostatistically significant（P＞0.05);3.2RT-PCR showed that there were positive correlations between the expression ofHMGB1mRNA and TLR4mRNA in three groups（r=0.567，P0.01）; positivecorrelations between the expression of HMGB1mRNA and NF-Bp65mRNA in threegroups （r=0.683， P0.01）； positive correlations between the expression ofNF-Bp65mRNA and TLR4mRNA in three groups（r=0.729，P0.01）.4.1Levels of HMGB1、TLR4、NF-κBp65in women with preeclampsia significantlyhigher than control group(P0.01); Levels of HMGB1、TLR4、NF-κBp65in womenwith severe preeclampsia higher than with mild preeclampsia (P＜0.05);4.2there were positive correlations between the Levels of NF-κBp65and TLR4inblood serum in three groups（r=0.549，P0.01）; positive correlations between theLevels of HMGB1and TLR4in blood serum in three groups（r=0.668，P0.01）；positive correlations between the Levels of NF-κBp65and HMGB1in blood serum inthree groups（r=0.655，P0.01）.Conclusion: When TLR4identified as inflammatory cytokines and damageassociated molecular pattern of endogenous ligand HMGB1, its downstream signalingpathway open, aggregating myd88, activating NF-κB and turned into nuclear.An awful lot of inflammatory factor caused by placental vascular injury, would promotethe progress of the disease. Thes gnaling pathway plays an important role in thepathogenesis of preeclampsia and perinatal prognosis.