Study On Cerebral And Hepatic SOD And MDA Level In Neonatal Rats With Intrauterine Growth Restriction

Fetal growth restriction (FGR) is failure of the fetus to achieve his or her intrinsic growth potential, due to anatomical or functional disorders in the feto-placental-maternal unit. FGR is the second cause of perinatal death of newborn infants and can complicate up to 3-10% of all pregnancies. FGR is associated with increased short- and long-term childhood morbidity and mortality, and a range of cardiovascular and metabolic diseases later in life. Apart from these physical problems, fetal growth restriction is also associated with neurodevelopment changes. The underlying mechanisms of brain damage in fetal growth restriction are complex and still not wholly understood.Recently, some reports have suggested a strong link between oxidative stress and brain damage. Because fetus with growth restriction experiences long time relative hypoxia and low nutrition supply, we postulated that fetus with IGF may also suffer from oxidative stress, which may be related to brain damage.Our objects are to develop an animal model that would resemble human FGR caused by utero-placental insufficiency (part one), and to study changes of superoxide dismutase (SOD) and malondialdehyde (MDA) level in brain and liver tissue ofneonatal rats with intrauterine growth restriction (part two).Part one: Development of fetal growth restriction model in ratsMaterial and methods1. Animal:Pregnant SD rats with gestational age of 17 days.2. Methods:On day 17 of gestation, the right uterine and ovarian arteries were occluded for 30 minutes in experimental rats to induce fetal ischemia/reperfusion (I/R group). In control group, the animals were sham operated without the occlusion of uterine and ovarian arteries. On day 21, the pregnant rats were performed with C/S and all live pups were scaled immediately. Fetal brain and liver were rapidly removed, weighted, and frozen in -70℃.3. Definition of FGR:FGR were defined if its body weight was below two standard deviations of the mean of control. The remaining rats in I/R group were defined as Non-FGR.4. Comparisons:Mortality of fetus; the incidence of FGR in I/R and control groups; the incidence of FGR in ischemic horn and non-ischemic horn of I/R group; fetal body and organ weights, and cerebrum/liver weight ratio.5. Statistics:Results are presented as mean ± SEM. All data were evaluated with SPSS 11.0. P < 0.05 was considered to be statistically significant.Results1. A total of 16 pregnant SD rats were enrolled, 8 for I/R surgery and 8 for control.2. One pregnant rat died accidentally during anesthesia in control group.3. The mortality of fetus was 4.55% (5/110) in I/R group and 3.19% (3/94) incontrol group respectively (P>0.05).4. The incidence of FGR was 21.9% (23/105) in I/R group and 3.3% (3/91) in control group respectively (P>0.05). In I/R group, the incidence of FGR was 22.22% (12/51) in ischemic horn and 20.37% (11/54) in non-ischemic horn (P>0.05).5. Cerebrum and liver weight decreased significantly in FGR group, compared with that in non-FGR group and control group (P<0.01), while the cerebrum/liver weight ratio in FGR group increased significantly compared with that in other two group (P<0.01).Conclusion1. Ischemia/reperfusion induced by clamping arteries of right uterine horn can cause FGR in both ischemic horn and the non-ischemic horn in pregnant rat.2. The model is more suitable for study because of its high incidence of FGR, easier operation, and more survivors.Part Two: Study on cerebral and hepatic SOD and MDA level in neonatal rats with intrauterine growth restrictionMaterials and methods1. Materials:Cerebral and hepatic tissues collected during part one were selected by randomization.2. Methods:SOD was measured by xanthinoxidase method and MDA by thio-barbituric acid method.3. Grouping:FGR group: FGR from I/R group (n=20), Non-FGR group: Non-FGR from I/R group (n=25); Control group: Non-FGR from control group of part one (n=25).4. Comparison:SOD level in cerebral and hepatic tissue in different groups; MDA level in cerebral and hepatic tissue in different groups.5. Statistics:Results are presented as mean ± SEM. All data were evaluated with SPSS 11.0. P < 0.05 was considered to be statistically significant.Results1. Cerebral SOD level in different groups were not statistically significant (P>0.05) (FGR group: 53.564 ±17.510 U/mgprot; Non-FGR group: 57.093±16.309 U/mgprot; Control group: 54.825±12.021 U/mgprot).2. SOD in hepatic tissues in different groups were not statistically significant (P>0.05) (FGR group: 94.912 ±13.472 U/mgprot; Non-FGR group: 95.320±17.578 U/mgprot; Control group: 103.271±14.477 U/mgprot).3. Cerebral MDA level in FGR group was statistically higher than that in Non-FGR and control group (P<0.01) (FGR group: 2.510 ±0.785 nmol/mgprot; Non-FGR group: 1.536±0.419 nmol/mgprot; control group: 1.438 ±0.555 nmol/mgprot).4. Hepatic MDA level were not statistically different in three groups (P>0.05). (FGR group: 4.939 ±0.972 nmol/mgprot; Non-FGR group: 5.364±0.990 nmol/mgprot; Control group: 5.456 ±0.906 nmol/mgprot).Conclusion1. There are no obviously changes of SOD in cerebrum and liver tissue in neonatal rat with FGR.2. The elevation of MDA in cerebrum, but no change in liver tissue, indicates that the brain is more sensitive to oxidative stress in fetal rat with FGR.