RESUMEN
Objective To study the roles of advanced glycation end products and its receptor on fetal brain injury of gestational diabetes mellitus (GDM) rats.Methods Twenty one adult pregnant Wistar rats were administered streptozotocin (STZ) intraperitoneally to induce GDM rats model.The fourteen pregnant rats were divided into two groups according to the fasting glucose on the 3rd day of pregnancy:severe GDM group with the fasting glucose ＞ 16.7 mmol/L and mild GDM group with the fasting glucose between 6.7 - 16.7 mmol/L Another seven pregnant rats were chosen as the severe GDM and intervention with micronutrient group,receiving gavage with micronutrient during the whole pregnancy.Five control rats received the same volume of citric acid buffer.All the pregnant rats were tested fasting glucose from the tailvein and their weight on the pregnant day 3,13 and 19.Maternal serum levels of AGE were measured by ELISA and RAGE levels in the embryonic brain tissues were tested by immunohistochemistry.Results ( 1 ) There was no statistically significant difference of pre-pregnancy fasting glucose level among all groups (P ＞ 0.05 ).The fasting glucose levels on the 3rd day and the mean fasting glucouse level of pregnancy in the severe GDM group and the severe GDM and intervention with micronutrient group were higher than those of the control group ( P ＜0.05 ).And there was no significant difference between the severe GDM group and the severe GDM and intervention with micronutrient group (P ＞0.05 ).(2)The serum AGE levels in the severe GDM group and the mild GDM group were( 1037 + 38) ng/L and( 880 ± 34) ng/L respectively,with no significant difference ( P ＞ 0.05 ).The serum AGE levels in the control group and the severe GDM and intervention with micronutrient group were (857 ± 32 ) ng/L and (988 ± 37 ) ng/L,and the difference was statistically significant ( P ＜ 0.05 ).The serum AGE levels in the severe GDM and intervention with micronutrient group and in the mild GDM group had no significant difference ( P ＞ 0.05 ).( 3 ) The serum AGE levels in the severe GDM group,mild GDM group and the control group were positively associated with the mean glucose level of pregnancy ( r =0.603,P ＜ 0.05 ) and the grlucose on the 3rd day of pregnancy (r =0.704,P ＜ 0.05 ).(4)The fetal brain nerve cell number and morphology in the control group were normal.While in the mild GDM group fetal brain nerve cells decreased,the proliferation and swelling of glial cells were seen.In the severe GDM group and the severe GDM and intervention with micronutrient group,the fetal brain cells furtherly reduced,and large vacuole around the cells,deformation and debris of the cells were seen. Glial scar formation was visible in some fetal brain tissues.There was a few RAGE expression in the control fetal brain tissues.In the mild GDM group and the severe GDM group,RAGE expression increased significantly.And the RAGE expression intensity in the severe GDM and intervention with micronutrient group was between the severe and the mild GDM groups.Conclusions( 1 ) Abnormal fetal brain development of GDM rats was associated with the increase of maternal serum AGE and the enhancement of RAGE expression in fetal brain tissues,which suggested that AGE/RAGE pathway may play an important role in the fetal brain injury of GDM rats.(2) Micronutrients can reduce the brain damage of GDM fetuses.
RESUMEN
Objective To establish and assess the high-birth-weight offspring model of the diabetic rat induced by stueptozotocin,and the long-term metabolic impact of maternal hyperglycemia of those offsprings.Methods Streptozotocin (STZ,25 mg/kg) was given to Wistar rats (G group,n =14) once intraperitoneally to induce maternal hyperglycemia model (blood glucose between 10-20 mmol/L),and there still had a number of rats defined as severe hyperglycemia model group (SG group,n =5).The Control group (C group,n =7) were given the same volume citrate buffer solution.The body weight and blood glucose were recorded,and the lavaging glucose tolerance test (LGTT) was performed by a glucose meter in the gestation.The offsprings were corresponding allocated into 2 groups,and the birth weight were recorded.All the offsprings were observated body weight,blood glucose blood pressure (male rats only),and so on.Results (1) The blood glucose of G group (16.8 ±5.4 mmol/L) and SG group (20.5 ±5.6 mmol/L) were increased significantly as compared with C group (7.0 ± 1.4 mmol/L) 5 days after the model was established (P ＜ 0.01) ; and the average blood glucose of G group (16.6 ± 3.4 mmol/L) and SG group (23.8 ± 1.5 mmol/L) increased too as comparede with C group (5.8 ± 1.1 mmol/L),the difference was significance according to statistics (P ＜ 0.01).(2) According to the LGTT result,which operationed on generation day 4 and day 10,the blood glucose of every time point of G group were increased significantly as compared with C group (P ＜ 0.01).(3) The male and female birth weight of G group was remarkably higher than the C group and the SG group (P ＜ 0.05),and the blood glucose of SG /G/C group was (6.5 ±1.2) mmol/L,(4.1 ± 0.8) mmol/L,(4.1 ± 0.8) mmol/L respectively,according to the statistics results,the difference between SG group and G/C group respectively both remarkable (P ＜ 0.05).(4) The body weight,Lee's index,fat weight,and the fat weight of mass ratio in C group mother rats after lactation presented dressed compared with the SG group (P ＜ 0.05),and so as to the G group compared with the SG group (P ＜ 0.05).(5) In the female offsprings of G group,the birth weight was remarkably increased compared with the C group (P ＜ 0.05) ; the body weight of the female offsprings presented an increased trend compared with the C group since the 12 weeks,but had no statistical significance; there were significant differences of body weight between G group and C group since 15 weeks (P ＜ 0.05),and the trend kept up until 26 weeks; in the male offsprings of G group,the body weight on birth day and 4 weeks had a marked rise compared with the C group (P ＜ 0.05) ; and from then on,the body weight of the male offsprings presented an increased trend compared with the C group,but had no statistical significance until 26 weeks (P＞0.05).(6) In G group,the blood glucose on 30 min and 60 min of LGTT in female offsprings were increased than the C group since 20 weeks (P ＜ 0.05) ; the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P ＜ 0.05) ; in G group,the blood glucose on 30 min of LGTT in male offsprings was remarkably incrcascd than the C group since 16 weeks (P ＜0.05) ; the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P ＜ 0.05).(7) The blood pressure of male offsprings in G group had a marked rise on 12 weeks compared with the C group (P ＜ 0.05) ; from then on the blood pressure of G group kept up a rise trend until 26 weeks,but had no statistical significance (P ＞0.05).Conclusion The diabetic high-birth-weight rat model could be duplicated with STZ (25 mg/kg) once intrapertoneally on the first day of gestation,which were observed some evidently metabolic changes in weight,glucose tolerance and blood pressure.These results could represent an forward step in the clinical study of human gestational diabetes mellitus and their macrosomia babies,which may suffer some metabolic disease in their later life.