| Gestational diabetes mellitus(GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. It is one of the common complications of pregnancy in perinatal period. The prevalence is increasing year by year.GDM seriously endanger health of mother and fetus. The dysfunction of glycometabolism during pregnancy can effect implantation of embryo and lead to abortion.The development of GDM is related to insulin resistance ( IR ).Nuclear factor-κB (NF-κB) is an important transcription regulation factors, participating in the process of signal transductions in cells and regulation of gene expression,and playing a vital role in immunity, inflammatory reaction, cell growth and differentiation. Inflammatory factor , such as tumor necrosis factor-α(TNF-α), oxidative stress and free fatty acid(FFA) can activate NF-κB. NF-κB signaling pathway can interfere with the transduction of insulin signal, leading to insulin resistance. Glucose transporter-4(GLUT-4) is the key element in insulin signal transduction pathway. It provids glycose for all types of cells It is also related to IR. Uterus is not.only a female generative organ,but also a organ which is related to energy metabolism. Endometria have insulin signal transducer and metabolic enzyme. Insulin can stimulate endometrial tissue to use glucose,which is necessary for endometrial tissue to development and differentiation.It is also necessary for fetus to growth during pregnancy.Objective:(1) Establish the animal model of GDM to observe the numbers of embryo implantation and abortion of rats with GDM.(2) To explore the expression of TNF-α,FFA,NF-κB,GLUT-4 in the endometrium of rats with GDM and the effect of pyrrolidine dithiocarbamate(PDTC) ,an inhibitor of NF-κB.(3) To determine the relationship between GLUT-4 and NF-κB in the pathogenesis of insulin resistance in endometria of rats with gestational diabetes mellitus.Methods:(1) Thirty Sprague-Dawley rats were randomly divided into 3 groups : normal pregnant control group, GDM group and PDTC group with 10 rats in each group. GDM model was induced by intraperitoneal injection of streptozotocin(STZ).PDTC group was injected intraperitoneally of PDTC with a dosage of 40mg/kg. Their blood glucose and body weights were measured before inject STZ and inject STZ 3 days later and on the 20-day of pregnancy.The rats were sacrificed on the 20-day of pregnancy before delivery.The numbers of embryo implantation and abortion were observed. (2) The pathological of endometrial were measured from routine HE staining.(3) ELISA techniques and colorimetry was employed to measure the expression of TNF-a and FFA in the endometrium of rats with GDM.(4) The expression of NF-κB,GLUT-4 in rats uterus was measured by immunohistochemical staining and western blot. RT-PCR was used to examine the expression of GLUT-4 mRNA in rats endometrium.Results:(1) It was observed that all rats have gained weight during pregnancy.Compared with NC group,GDM group and PDTC group had lower whight level(P< 0.01).Their blood glucose was significantly higher than that of the NC group(P<0.01).The numbers of embryo implantation of GDM group was lower (P< 0.01) and the numbers of abortion of GDM group was higher than that of NC group(P<0.01).Compared with GDM group,PDTC group have higher embryo implantation numbers(P< 0.01).(2) The pathological of endometrial were measured from routine HE staining.The results show that there are significantly difference in the numbers and sizes of endometrial gland between GDM group and NC group.(3) The expression of TNF-a and FFA in GDM group were increased than NC group(P<0.01).Compared with GDM group,The expression of TNF-a in PDTC group were decreased(P<0.01).(4) Compared with NC group,the expression of NF-κB in GDM group were increased(P<0.01),the expression of GLUT-4 in GDM group were decreased (P<0.01).Compared with GDM group,the expression of NF-κB in PDTC group were decreased (P<0.01),the expression of GLUT-4 in PDTC group were increased (P<0.01).The GLUT-4 mRNA levels of GDM group were decreased than NC group(P<0.01), Compared with GDM group,the levels of GLUT-4 mRNA in PDTC group were increased (P<0.01).The expression of TNF-a,FFA were positive correlation with the expression of NF-κB (P<0.01).The expression of NF-κB was negative correlation with the expression of GLUT-4(P<0.01).Conclusions:(1) In this research,we establish the animal model of GDM by intraperitoneal injection of STZ.During pregnancy,the weight of GDM rats was significantly lighter than normal rats,the blood glucose of GDM rats was significantly higher than normal rats,which proved that we have successfully established the GDM model.(2) The expression of TNF-a and FFA in the endometrium of GDM rats were increased,which could activate NF-κB.The expression of TNF-a,FFA were positive correlation with the expression of NF-κB.The expression of NF-κB was increased in uterus of GDM rats.(3) The expression of GLUT-4 were decreased in GDM rats.Inhibition of NF-κB activity could increase the expression of GLUT-4 in uterus of GDM rats.This demonstrate that the occurrence of GDM in rats with uteru insulin resistance may be related with the intervention of NF-κB activity on the down regulation of the expression of GLUT-4.NF-κB and GLUT-4 may play important roles in uteru insulin resistance and related with embryo implantation and abortion.
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