| Objective:The rat model of intrauterine growth retardation (IUGR) was established by low-protein diet taken by the mother during the whole time of pregnancy. To compare the difference of body weight of IUGR young rats given different contents of protein in diet during 3 weeks after birth, and to determine the differences of fasting glucose, fasting insulin in serum, and to compare the different expression of hepatocyte nuclear factor -4alpha(HNF4alpha), phosphoenolpyruvate carboxykinase (PEPCK) in liver, in order to investigate the possible mechanism of long-term metabolic syndrome of IUGR rats, and to provide a theoretical basis of early nutritional support for IUGR/SGA patients.Methods:The experimental maternal rats are age-appropriate (Body weight 200-250g, age 70-80 days) SD rats. All the maternal rats are fed by low-protein or normal-protein diet during the whole time of pregnancy. IUGR newborn rats were randomly divided into three groups:IUGR standard protein group, IUGR low protein group and IUGR high protein group, fed by standard protein diet, low-protein diet, or high protein diet respectively for 3 weeks after birth; then changed to standard diet until the end of experiment after weaning. Normal diet was fed in rats of control group, and maternal rats were fed by standard diet, pups were also fed by standard diet after birth until the end of experiment. The rats’ body weight was measured at the 0 weeks (12 hours after birth),4 weeks and 12 weeks after birth respectively, using high-precision electronic weighing scales. The fasting glucose and fasting insulin in serum of rats were measured by ELISA kit at three time points in each group. The expressions of HNF-4a and PEPCK in the liver of rats were detected by RT-PCR and Western blotting technique. The results were analyzed, using statistical software SPSS 19.0. P<0.05 was considered statistically significant.Results:1.Still birth rate:The still birth rate of rats was 16.4%(33/201) in the low-protein diet group and 4.5%(4/88) in normal-protein group. The differences was significant (P<0.05).2. The body weight of rats was 5.011±0.436g and 6.090±0.553g in IUGR group and the normal-protein group respectively. The birth weight of rats in IUGR group was significantly lower than that in normal-protein group (p<0.05).3. The incidence rate of IUGR:IUGR incidence in the IUGR group was 51.2%(86/168), which were significantly higher than the normal-protein group (8.3%; 7/84)(p<0.05). 4. Body weight (g):Rats’body weights at the 0 week were 4.685±0.191g and 6.331±0.382g in IUGR standard protein group and normal-protein group respectively. The difference was statistically significant (P<0.05). The rats’ body weights at 4 weeks were 49.624±7.594g,45.387±4.921g,27.213±2.556g and 60.323±3.098g in normal-protein group, IUGR standard protein group, low protein group and high protein group respectively. The weight had no difference between normal-protein group and IUGR standard protein group. The weight of rats in IUGR low-protein group was lower than that of normal-protein group, IUGR standard protein and high protein group, and the weights of rats in normal-protein group, IUGR standard protein group were lower than that of IUGR high protein group. The rats’ body weight at 12 weeks were 236.588±23.876g,262.125±18.555g,181.538±12.897g and 247.625 ±15.954g in normal-protein group, IUGR standard protein group, low protein group and high protein group respectively. The weight of rats in IUGR standard protein group was higher than that of normal-protein group and IUGR low protein group, and the weights of rats in normal-protein group was higher than that of IUGR low protein group. The weight had no difference between normal-protein group and IUGR high protein group.5. Fasting plasma glucose (mmol/L):The fasting plasma glucose at the 0 week had no difference between normal-protein group and IUGR standard protein group. The fasting blood glucose at 4 weeks of 4 groups had no difference. At 12 weeks, the fasting plasma glucose of rats in IUGR standard protein group and low protein group were higher than that of normal-protein group, and the fasting plasma glucose of rats in IUGR low protein group was higher than that of IUGR standard protein group, and the fasting plasma glucose had no difference between normal-protein control group and IUGR high protein group.6. Fasting insulin (mU/L): The fasting insulin at the 0 week had no difference between normal-protein group and IUGR standard protein group. In 4 weeks, the fasting insulin of rats in IUGR low-protein group was higher than that of other groups, and that of other groups were no difference. In 12 weeks, the fasting insulin in IUGR standard protein group, low protein group were higher than that of normal-protein control group, IUGR high protein group, and the fasting insulin in IUGR low protein group was higher than that of IUGR standard protein group.7. The relative content and protein expression relative amount of HNF-4α mRNA:The expression of HNF-4α mRNA at the 0 week in IUGR standard protein group was lower than that of normal-protein group. In 4 weeks, the expression of HNF-4α mRNA in IUGR standard protein group, low protein group and high protein group were lower than that of the normal-protein group, and the expression in IUGR low protein group was lower than that of IUGR standard protein group and high protein group. In 12 weeks, the expression of HNF-4α mRNA in IUGR standard protein group, IUGR low protein group were lower than that of normal-protein group and IUGR high protein group, and the expression had no difference between normal-protein group and IUGR high protein group.8. The relative content and protein expression relative amount of PEPCK mRNA:The expression of PEPCK mRNA at the 0 week in IUGR standard protein group was higher than that of normal-protein group. In 4 weeks, the expression of PEPCK mRNA in IUGR standard protein group, low protein group and high protein group were higher than that of the normal-protein group, and the expression in IUGR low protein group was higher than that of IUGR standard protein group, and the expression IUGR standard protein group was higher than that of IUGR high protein group. In 12 weeks, the expression of PEPCK mRNA in IUGR standard protein group, IUGR low protein group were lower than that of normal-protein group and IUGR high protein group, and the expression in IUGR low protein group was higher than that of IUGR standard protein group, and the expression had no difference between normal-protein group and IUGR high protein group.Conclusion:1. IUGR pups after birth through early high-protein diet can complete weight of catch-up growth; it does not appear glucose metabolism occurs.2. Intrauterine malnutrition environment can cause HNF-4α gene expression decreased and PEPCK gene increased, and is the basis of IUGR rats’ adult metabolic syndrome. |
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