The Study On The Correlation Between TNF-a NF-KBp65PAI-1Concentrations And The Pathogenesis Of The GDM

Objective:Gestational diabetes mellitus (GDM) is defined ascarbohydrate intolerance of variable severity with onset or first recognitionduring pregnancy.Its incidence was approximately1-14%and had grown inrecent years. Increasing incidence and complex complications of GDM had anegative impact on the maternal and infant health, However, the mechanism ofGDM is not identified clearly. At present,there have many theories about themechanism of the GDM,such as the theories of gene susceptibility, oxidativestress, insulin resistance, cytokine distribution and expression abnormal, et.al.GDM was closely related to Type2diabetes,and even say it was the earlyphase of the type2diabetes.A large number of data showed that inflammationfactors have closely correlation with the onset and the course of type2diabetes. On the basis of it,we concluded the inflammation factors might playa role in GDM.The overseas literatures reported the existence ofpro-inflammatory factors and the possible involvement of a hypercoagulablestate in the pathogenesis of gestational diabetes mellitus (GDM).The domesticliteratures also reported the existence of inflammatory factors in thepathogenesis of GDM. There are many reports about theTNF-a,NF-KBp65,PAI-1in the Cancer, cardiovascular and the diabetescompared to that in the GDM.TNF-a is a cytokine which is secreted byvarious inflammatory cells and the immune cells. It mainly exhibits biologicaleffect through binding to its receptors on the cell membrane. In recent years, Itwas found that TNF-a and TNFR-1together participate in signal transductionwhich related to almost all functions. TNF-a together with TNFR-2inducedthe onset of insulin resistance in Ⅱdiabetes by various means. Insulinresistance is also one of the pathogenesis of GDM. The literatures reported theexistence of oxidation and antioxidant imbalance and the involvement of TNF-a,NF-KBP65expression in the serum with late-onset GDM.Nuclear transcription factors p65(NF-KBp65), belong to rel-proteinfamily, is a multiplex transcription factor. Based on findings todate,NF-KBp65is the most widespread, the most important role of NF-KBcombination form. It can adjust the expression and synthesis of variousinflammatory factors, adhesion molecules and growth factors. NF-KBp65playa key and core role in the immune adjustment and inflammatory reaction.Atrest,heterologous dimers of NF-KB (P65-P50) combined with NF-KBinhibiting protein (IKB) and existed in cytoplasm inactively..When NF-KBwas stimulated by inflammation factors such as TNF-a IL-1,IL-2whichmade the NF-KB inhibiting protein N ser the phosphorylation by activatingthe NF-KB inhibiting protein kinase and then the NF-KB is activated. Theactivated NF-KB can make a shift into the nucleus and adjust the expressionof the inflammation factors such as the TNF-a,IL-1,IL-2at transcriptionallevel.The plasminogen activator inhibitor1(PAI-1)belong to serine proteaseinhibitors superfamily, is an inflammatory protein that produced by variouscells. It is the main inhibitor of UPA and the most important regulator offibrinolytic activity.PAI-1can inhibit fibrinogen degradation, promotefibrinogen deposition in blood vessel wall and stimulate smooth muscle cellproliferation. In addition to its classic fibrinolytic function, PAI-1is was animportant factor that can play an important role in the body'simmunization,inflammation and infection control. High concentrationexpression of PAI-1in early inflammation had effect on the inflammatory cellschemotaxis and participated in the formation of the inflammatory cytokinenetwork. In recent years,a great deal of research shows that PAI-1closelyrelate to the activation and migration of inflammatory cells and express ininflammatory cells such as mononuclear cells, neutrophils, mast cells,activated T lymphocytes. By studying the expression of TNF-a, NF-KBp65,PAI-1in maternal serum and placental tissue of GDM, the experimentanalyzed the relationship between these cytokines and the onset of GDM and then provided the theory basis for further study of the pathogenesis of GDMMethods: From November2010to May2011,44pregnant women in thematernity ward. Of The Second Hospital Affiliated to Hebei MedicalUniversity were recruited, including22with GDM(test group) and22withnormal glucose tolerance test(control group). The pregnant women whoparticipate in the experiment performed regular antenatal examination andgave birth in The Second Hospital Affiliated to Hebei MedicalUniversity.These pregnant women eliminate the other diseases, such asliver and kidney dysfunction, infections, hypertensive disorder complicatingpregnancy, coronary heart diseases., et al. There were no significantlydifference among these pregnant women in age, BMI, delivery gestational ageet al. The diagnostic criteria of GDM was made. According to the standardissued by IADPSG in2010.Antecubital vein blood was collected on an emptystomach before birthing,the serum was separated and preserved at-70℃refrigerator for later use.The placenta tissue was took near the umbilical cordaway from bleeding, infarction and calcification area after t delivery of theplacenta tissue immediately.Its size was about1.5cm×1.5cm×0.5cm.It waspreserved in4%formaldehyde solution after washed by physiological salinefor future use.Enzyme-linked immunosorbent assay and.Immunohistochemical method were used to determine the expression ofTNF-a NF-KBp65PAI-1in the serum and placental tissue which werecompared and analyzed between the test group and the control group.Correlations of TNF-a NF-KBp65PAI-1with another in the serum and withclinical index were analyzed.Results: The serum concentrations of TNF-a PAI-1in the test group weresignificantly higher compared with the control group, They were(185.83±123.33)mg/L vs.(86.14±122.66) mg/L,(349.36±243.51) mg/Lvs.(155.45±125.97) mg/L. Differences of the NF-KBp65concentrations in theserum between the two groups were not statistically significant. Theywere.(421±136.23mg/L,vs.435±115.66mg/L).TNF-a concentrations waspositively correlated with PAI-1concentrations.(r=0.866), Among blood sugar at each point of OGTT, fasting blood sugar, fasting insulin and insulinresistance index,Insulin resistance index had the biggest impact on theconcentrations of TNF-a and1-h plasma glucose value of OGTT had thebiggest impact on the concentrations of PAI-1.Expression positive rate of theTNF-a NF-KBp65PAI-1in the placenta of the test group were significantlyhigher compared with the control group, They were72%vs.18%,68%vs.20.9%,62%vs.22%. The difference of the expression positive ratebetween the two groups were statistically significant.Conclusion: The expression of TNF-a NF-KBp65PAI-1in the serumand placental in GDM may play a role in the onset and the course of GDM.