Role Of Chemerin 、 TNF-α In The Pathogenesis Of Gestational Diabetes Mellitus

Gestational diabetes mellitusus(GDM)is defined as the first occurrence of abnormal glucose tolerance during pregnancy,which is one of the most common complications of pregnancy,including undiagnosed diabetes during the first pregnancy.Although women with GDM usually recovered after delivery,they may be still at high risks in 2TDM.Chemerin is a kind of adipokine which could regulate adipocyte differentiation and function.It may represent a link between obesity and vascular inflammation,and associates with insulin sensitivity in obese people.However,there are fewer studies on the relationship between chemerin and GDM.TNF-α is an adipokine,as well as a cytokine,that mediates multiple inflammatory and immunomodulatory responses.Researchers have pointed out that TNF-α is involved in insulin resistance,but the interaction between TNF-α and chemerin under the condition of GDM is still in controversy.In this study,Firstly,the expressions of chemerin and TNF-a in peripheral and umbilical cord blood of GDM and NGT women were measured.At the same time,the expression level of Chemerin and TNF-α in placental tissues and umbilical cord tissues was determined to explore the role of Chemerin and TNF-α in GDM and its effect on the fetus.PART ⅠSerum chemerin and TNF-α levels in Peripheral and umbilical Cord Blood of the third trimester pregnancyObjective:To detect the expression of chemerin and TNF-α in serum and umbilical cord blood of GDM and NGT in the third trimester pregnancy,and explore the role of the two adipokines in the pathogenesis of GDM.Methods:This study included 100 pregnant women who received routine antenatal care in Hebei General Hospital,and gave birth by cesarean from October 2016 to October 2017.According to the results of 75 g glucose tolerance test(OGTT),Pregnant women were divided into GDM group(n = 50)and normal pregnancy group(NGT,n = 50),and both two groups of the pregnant women with single pregnancy.The fasting blood glucose of each group were detected by glucose oxidase method.Radioimmunoassay was used to detect fasting insulin(FIN)levels,and then calculate insulin resistance index(HOMA-IR)in each group.Total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)and low density lipoprotein(LDL)were measured in each group.At last,the levels of chemerin and TNF-α in serum were measured by ELISA.Results:1 The TG levels of serum lipids in GDM group and NGT group were 3.37 ±1.41)mmol/L and 2.59 ±0.85 mmol / L,respectively.The difference was significant(P < 0.05),but there was no statistical difference between the two groups(P > 0.05).2 The mean fasting blood glucose level in the GDM group was(4.89 ±0.61)mmol / L duringthe last trimester of pregnancy(P < 0.01),higer than the fasting blood glucose level(4.53 ±0.61)mmol / L in the NGT group(P < 0.01).3 The fasting insulin and insulin resistance index(HOMA-IR)in GDM group were(14.63 ±11.80)and(2.98 ±1.63),respectively.The fasting insulin and insulin resistance index(HOMA-IR)in NGT group were(10.82 ±3.38)and(2.16 ±0.73),respectively.The difference between the two groups was statistically significant(P < 0.05).4 The serum chemerin levels of GDM group and NGT group were {(1.61 ±0.72)vs(1.58 ±0.84)} ng / ml,respectively.There was no significant difference between the two groups(P > 0.05).The chemerin level in cord blood of GDM group was(7.20 ±2.51)ngml / ml.The chemerin level in cord blood of NGT group was(5.58 ±1.50)ng / ml,and the chemerin level in cord blood of GDM group was significantly higher than that of NGT group(P < 0.01).5 The serum TNF-α level in GDM group was(130.16 ±61.75)ng / ml,while the TNF-α level was(84.50 ±36.96)ng / ml in NGT group.Compared with NGT group,the serum TNF-α level in GDM group was significantly higher than that in NGT group(P < 0.01).And there was no significant difference in the level of TNF-α in cord blood between the GDM groups and NGT group{(78.78 ±34.68 and 92.97 ±43.59)ng / ml,P > 0.05}.In both NGT and GDM groups,the level of chemerin in umbilical cord blood increased significantly than maternal blood(P < 0.01).6 The level of serum chemerin in NGT group was positively correlated with the level of TG(r=0.448,P < 0.005)and the level of serum VLDL(r= 0.355,P < 0.034).Serum TNF-α levels in GDM group were positively correlated with fasting blood glucose(FBG)in the third trimester of pregnancy(r=0.335,P=0.012;r=0.395,P=0.005).There was a positive correlation between serum TNF-α level and serum chemerin level(r:0.344,P=0.015).But there was a negative correlation between the levels of cord blood chemerin and TNF-α in GDM group.No significant correlation between the remaining indicators.Conclusion:1 The level of chemerin in peripheral blood of NGT group in late pregnancy is related to the metabolic index of blood lipid,which suggests that chemerin is involved in the regulation of energy metabolism in pregnancy and maintains the homeostases of maternal metabolism.2 The level of chemerin in umbilical cord blood in GDM group was significantly higher than that in NGT group,indicating that the neonates in GDM patients may be in a state of high inflammation.It is inferred that chemerin is related to the complication of offspring.3 The level of TNF-α in GDM group was significantly higher than that in NGT group,which supported the theory that oxidative stress and inflammatory reaction were involved in the occurrence of GDM.4 There was a positive correlation between serum chemerin level and serum TNF-α level in GDM patients in late pregnancy,but a negative correlation between them in umbilical cord blood,which suggested that there was a certain relationship between them,which was not the same in adults and fetuses.PART ⅡExpression of chemerin and TNF-α mRNA and protein in placenta and umbilical cordObjective:To detect the expression of chemerin,TNF-α mRNA and protein in placental and umbilical cord tissues of GDM and NGT,and to explore the role of chemerin and TNF-α mRNA in the pathogenesis of gestational diabetes mellitus(GDM)and their effect on fetal growth.Methods:This study recruited 100 pregnant women who received gave birth by cesarean section from October 2016 to October 2017.Pregnant women were divided into GDM group(n = 50)and normal pregnancy group(NGT,n = 50),and both two groups were single pregnancy.The placenta and umbilical cord tissues were collected during elective cesarean section.the expression of chemerin and TNF-α mRNA in placenta and umbilical cord were detected by fluorescent quantitative PCR(real-time FQ RT-PCR)method.And the expression of chemerin and TNF-α protein in placenta and umbilical cord were detected by Western blotting method.Results:1 In GDM group,the Chemerin and TNF-α mRNA in placenta and umbilical cord were(chemerin : 2.02±0.49,1.65±0.46 and TNF-α :2.32±0.55,1.33±0.43)respectively,and in NGT group,the Chemerin and TNF-α mRNA in placenta and umbilical cord were(chemerin : 0.84±0.30,0.88±0.22 and TNF-α :0.77±0.17,0.87±0.22),respectively.The difference between the two groups was significantly(P < 0.05).2 The expression of chemerin was significantly higher in the placentae than in the normal control group(6.71±1.53 and 2.64±0.59,P<0.01),and there is statistical difference.However,the protein of chemerin in umbilical cord tissue of GDM group was not significantly increased than that of NGT group(0.86±0.12 and 0.79±0.15,P=0.355).3 The expression of TNF-α protein in placenta and umbilical cord tissues in GDM group was significantly higher than that in normal control group(7.14 ±1.51 and 1.46 ±0.36,P < 0.01,9.29 ±1.75 and 3.37 ±0.99,P < 0.01).The difference was statistically significant.4 In GDM group,the expression of chemerin mRNA and protein in placenta was not related to neonatal weight(r=0.412,P=0.127;r=-0.224,P=0.593),while was positively correlated with TNF-α mRNA and protein expression(r=0.718,P < 0.01;r=0.927,P < 0.01).The expression of TNF-α mRNA and protein in NGT group and GDM group were positively correlated with neonatal weight(NGT 组:r=0.861,P < 0.05;r=0.836,P < 0.01 GDM 组:r=0.800,P < 0.05;r=0.912,P < 0.01).Conclusion:1 Both placental and umbilical cord tissues secrete chemerin and TNF-α during GDM.Chemerin acts mainly in the placenta as autocrine or paracrine,while TNF-α acts on the whole body.2 Chemerin can be secreted by the fetus itself.The high level of fetal Chemerin in GDM pregnant women is a reaction to the intrauterine high inflammatory state of the fetus.It may be one of the reasons that GDM pregnant women are susceptible to diabetes and other metabolic diseases.