| Objective: This study aims to understand the changes of placental fatty acid transport function and fetal growth and development in GDM environment of pregnant mice, and this study also aimed to explore the mechanism and influence of vitamin E on the expression of placenta fatty acid transporters and fetal growth in GDM mice.Methods: The animals were allowed free access to food and water at all times and maintained on a 12-hr light/dark cycle in a controlled temperature(20–25°C) and humidity(50±5%) environment. After a week of adaptation, breeding was conducted overnight in a 1: 2 ratio; mating was confirmed by presence of a vaginal mucous plug the following morning, which represented gestation day(GD) 0. Maternal gestational diabetes mellitus was induced by the intraperitoneal administration of streptozotocin(STZ)(Sigma-Aldrich, Castle Hill, Australia) in 0.1 M sodium citrate buffer. STZ was administered for 3 consecutive days commencing at GD6 at doses of 80, 80 and 80 mg/g bodyweight. Female mice were arbitrarily assigned to three groups: Control, GDM, GDM+vit E in a generalized randomized complete block design, with 12 mice per group. Control group: saline, 5 mg/kg d i.g.GDM mice in the Control group: normal saline, 5 mg/kg d i.g. Antioxidant supplement groups: vitamin E, 5 mg/kg d i.g. Dams were euthanized on GD18 by intraperitoneal injection of sodium pentobarbital and placentas were immediately collected.Results:(1) A single factor repeated measures ANOVA of the body weight of pregnant rats in different groups and times with showed that: Time effect of the corrected showed pregnant mice at different time difference was statistically significant(F = 243.188, P <0.001), weight of pregnant rats showed a rising trend in different time. Interaction of time and group showed different groups of pregnant rats are different(F = 4.290, P= 0.002); A single factor repeated measures ANOVA of theblood glucose of pregnant rats in different groups and times with showed that: Time effect of the corrected showed pregnant mice at different time difference was statistically significant(F= 3.425,P=0.039), weight of pregnant rats showed a rising trend in different time. Interaction of time and group showed different groups of pregnant rats blood glucose are different(F= 2.815,P=0.035); In GD18, levels of serum insulin of GDM mice were lower than Control mice(P<0.01), and those of Vit E were higher than GDM mice(P<0.05).(2) Fetal weight of GDM mice was significantly lower than those of Control mice(P<0.001), weight of fetuses after the Vit E intervention were more than those of GDM mice(P<0.05); Fetal body length of GDM mice was significantly less than those of Control mice(P<0.001), fetal body length of fetuses after the Vit E intervention showed significant difference(P<0.05);Fetal placental weight of GDM mice was significantly lower than those of Control mice(P<0.001), fetal placental weight of fetuses after the Vit E intervention showed no significant difference(P>0.05); Placental diameter of three groups showed no significant difference(P>0.05);Fetal blood of GDM mice was significantly less than those of Control mice(P<0.001), fetal blood of fetuses after the Vit E intervention showed no significant difference(P>0.05).(3) Compared with the Control mice, the SOD(P<0.01), GSH-px(P<0.05) in GDM mice serum were decreased, while MDA levels were significantly increased(P<0.01); Compared with the GDM mice, the SOD(P<0.01), GSH-px(P<0.05) significantly increased in the mice after the Vit E intervention, while MDA levels decreased significantly in the mice after the Vit E intervention(P<0.01).(4) Compared with the Control mice, the IL-6, IL-8 was significantly increased in GDM mice serum(P<0.01), and TNF-α levels, although relatively high, but it showed no significant difference(P>0.05);Compared with the GDM mice, the TNF-α, IL-6, IL-8 was significantly decreased in the mice after the Vit E intervention(P<0.05).(5) In immunoblotting experiments, compared with Control mice, the PPARγ, FATP1, FATP4 protein levels in GDM mice placenta were reduced(P<0.05), but FABP-pmprotein levels was raised in GDM mice placenta(P <0.05);Compared with the GDM mice, the PPARγ, FATP1, FATP4 levels were significantly increased in the mice after the Vit E intervention(P <0.05), FABPpm, CD36 levels were significantly decreased in the mice after the Vit E intervention(P <0.05);FATP2, FATP3 protein expression levels did not change.(6) In the RT-PCR test, compared with the Control mice, the expression levels of PPARγ, FATP1, FATP4 of m RNA was reduced in GDM mice placenta(P <0.01), but the expression levels of FABP-pm m RNA was raised in GDM mice placenta; Compared with the GDM mice, the PPARγ, FATP1 levels were significantly increased, and CD36 levels were significantly decreased in the mice after the Vit E intervention. Other protein m RNA expression did not change.(7) The results of HE-stained showed that GDM disordered arrangement of blood vessels and reduced blood cells; Immunohistochemical results showed that compared with the Control group, the mean density of PPARγ, FATP1 and FATP4 were decreased and the mean density of and CD36 and FABP-pm were increased; the Vit E intervention, the mean density of PPARγ, FATP1 and FATP4 were increased and the mean density of CD36 and FABP-pm were decreased.Conclusion: 1. Vitamin E have a protective effect on pancreatic β cell in STZinduced mouse. 2. Vitamin E may increases the activity of SOD, GSH-px concentration, and reduces MDA levels, lipid peroxidation, and thereby reduce the apoptosis of β cell; It inhibited the secretion of TNF-α, IL-1β, and raised the m RNA expression activate of PPARγ; It improved endothelial function, inhibited macromolecules peroxidation of DNA, lipid and protein, so that the apoptosis of the trophoblast cell rate declined, though Those ways the expression of fatty acid transport protein had enhanced, and LCPUFA transport capacity had increased. The results provided theory and guiding significance for the clinical treatment of some adverse symptoms induced by GDM. |
PDF Full Text Request