| Gestational diabetes mellitus(GDM)refers to abnormal glucose tolerance that occurs or is found during pregnancy.Increased insulin resistance in pregnant women and the loss of the function of islet B cells are two major causes that result in the development of GDM.Neutrophil gelatinase-associated lipocalin(NGAL)is a new type of adipocytokine and an inflammatory cytokine that is involved in different physiological and pathological processes.Recent studies have shown that NGAL levels are closely related to the development of hyperglycemia and insulin resistance.Tumor necrosis factor-alpha(TNF-?),as a factor mediating inflammatory responses,can be used as a predictor of insulin resistance.Objectives: The aim of the study was to investigate the potential role of NGAL and TNF-? in the pathogenesis of GDM and discuss he relationship between NGAL and fetal development by measuring the levels of NGAL and TNF-? in maternal blood and umbilical cord blood of GDM patients and normal pregnant patients,as well as the expressions of NGAL and TNF-? in placenta and umbilical cord tissue.Results: 1.Serum NGAL concentration levels were significantly higher in women with GDM than those in the control group both in maternal blood(4.80±1.99ng/ml vs.3.66±1.13ng/ml,P=0.001)and in cord blood(4.70±2.08ng/ml vs.3.85±1.44ng/ml,P=0.027).Serum TNF-? concentration levels were significantly higher in women with GDM than those in the control group(136.55±62.37ng/ml vs.93.13±38.87ng/ml,P<0.001).However serum TNF-? levels were lower in the GDM than those in the control group(71.58±36.43ng/ml vs.102.44±38.87ng/ml,P=0.001).Serum NGAL levels exhibited a positive correlation with FPG,FINS,and HOMA-IR.2.The expression of NGAL mRNA levels in placental(3.24±1.25 vs.1.30±0.57,P=0.001)and umbilical cord(2.02±0.41 vs.0.96±0.30,P<0.001)tissues were higher in GDM women than those in the control group.And the expression of TNF-? mRNA levels in placental [2.56(1.84,2.70)vs.0.79(0.61,0.99),P=0.001] and umbilical cord [1.16(1.03,1.64)vs.0.87(0.72,0.98),P=0.021] tissues were higher in GDM group than those in the control group.In the GDM group,the expression levels of NGAL mRNA in the placental tissues were significantly higher than those in the umbilical cord tissues(3.24±1.25 vs.2.02±0.41,P=0.020).3.NGAL protein levels were significantly higher in placental(1.22±0.39 vs.0.65±0.23,P<0.001)and umbilical cord tissues(0.67±0.10 vs.0.25±0.10,P<0.001)in the GDM group compared with the control group.And the TNF-? protein levels were significantly higher in placental [1.09(0.86,1.37)vs.0.28(0.25,0.57),P<0.001] and umbilical cord tissues [0.69(0.53,0.87)vs.0.11(0.10,0.16),P<0.001] in the GDM group compared with the control group.The expression levels of NGAL protein in placental tissues were significantly higher than those in umbilical cord tissues both in the control group(0.65±0.23 vs.0.25±0.10,P<0.001)and the GDM group(1.22±0.39 vs.0.67±0.10,P<0.001).4.In the GDM group,maternal serum NGAL levels positively correlated with cord blood NGAL(r=0.349,P=0.014),maternal serum TNF-?(r=0.311,P=0.029)and placental NGAL mRNA(r=0.848,P=0.008),protein expression levels(r=0.636,P=0.011),and birth weight(r=0.363,P=0.014).Conclusions: 1.The NGAL and TNF-? levels of serum and placenta tissues in GDM group was significantly higher than that in normal control group,and the serum NGAL levels of GDM patients was positively correlated with FPG,FINS,HOMA-IR and TNF-? levels.It is suggested that NGAL and TNF-? are involved in the development of GDM.2.The levels of NGAL in umbilical blood and cord tissue of GDM group was significantly higher than that of normal patients,indicating that NGAL was may related to fetal development.3.The expression levels of NGAL in placenta of GDM patients was positively correlated with the levels of NGAL in serum,suggesting that the excessive secretion of NGAL in placental tissue may be one of the reasons for the increase of serum NGAL levels,and may further induce insulin resistance. |
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