| Objective1.Intrauterine growth restriction (IUGR) is one of the common clinical problems. IUGRis not only closely associated with fetal birth weight, which results in diabetes,hypertension in adulthood, but also caused neurodevelopmental disorders, and evencerebral palsy. Therefore, it is very important to strengthen the research.2.Because cerebral damages of infants with IUGR starts during fetal development,postnatal treatment may not be adequate to achieve the desired effect. Thus, it is veryimportant to take prenatal interventions to improve the long-term prognoses of IUGRinfants.3.The present study aimed to explore the incidence of IUGR and the damage tofetal-newborn caused by IUGR, we investigated whether antenatal taurine supplementmight promote the brain development or not and explored the mechanism of thisprotection.Methods1.Epidemiological survey: the birth data of neonates were chosen from Beijing Obstetrics and Gynecology Hospital Affiliated to Capital University of Medical Sciences,First Hospital Affiliated to AnHui medical university, Hospital of Southern MedicalUniversity, Shaanxi maternal and Child Health Hospital, First Affiliated Hospital ofXinxiang Medical College and people’s hospital of Linyi from Jan1,2011to Dec31,2011. neonates hospitalized in our hospital. we analyzed the date and explored theincidence of IUGR; A retrospective case-control study was carried out to compare thedata between SGA and AGA, and explored the damage to fetal-newborn caused byIUGR. All the data were established in EXCEL and analyzed by spss16.0sofeware.2.Experimental research: Sprague-Dawley (SD) adult rats of clean grade were matedwith proper ratio every night and Microscopic examination of the vaginal secretionswas performed next morning. The day of sperm cell being discoveried in vaginalsecretions was designated as pregnant day0(P0). All pregnant rats were divided intocontrol, IUGR model, and IUGR+taurine groups. In the IUGR model group, animals were fed with low protein diet from gestation day1and continued throughout thepregnancy, on gestational day12, taurine was added into diet at a dose of300mg/kg/devery day until term delivery.Definition of IUGR: Birth weight was measured immediately after birth. The rats withan average birth weight more than two standard deviations lowered than the controlgroup were diagnosed of IUGR.The taurine levels of fetal rat brains were detected by High performance liquidchromatography-mass spectrometry. Neural cell apoptosis of the brain was detected byterminal deoxynucleoitidy transferase mediated nick end labeling TUNEL, changesin protein expression of glial cell line-derived eurotrophic factor(GDNF), cysteinylaspartate specific protease-3(caspase-3) and proliferating cell nuclear antigen(PCNA)were detected by immunohistochemistry, The level of mRNA expressions ofRas homolog gene A (RhoA) Rho-associated coiled coil-forming protein kinase2(ROCK2) and PCNA were detected by Real time-PCR.Results35418qualified neonates chosen from the six hospitals from Jan1,2011to Dec31,2011were enrolled into this study.3106neonatus were SGA, the incidence of SGA was8.77%, the SGA incidence of preterm infants (16.43%) was higher than that of terminfants (7.87%). The analysis of single risk factors of SGA revealed that the SGAincidence of females was significantly higher than that of males x2=6.285P0.05and5factors had significant difference, including hypertensive, abnormal amnioticfluid, amniotic fluid contamination, abnormality of umbilical cord x2=4.850-36.771, P0.05The complication incidence of SGA including anemia, cardiovascular diseaseand premature rupture of membrane was higher than that of AGA, but there was nosignificant difference.SGA accounted for9.77%among total patients composition ratio of which inhypoglycemia, asphyxia, hypoxic ischemic encephalopathy, gastrointestinal bleeding,congenital malformation, polycythemia vera, pneumorrhagia, apnea, congenital heartdisease, disseminated intravascular coagulation is higher than that of AGA2=4.06~45.06P0.05while composition ratio of SGA in jaundice was lowerthan that of AGA, there was no significant differerce in Composition ratio inScleredema, pneumonia, Respiratory distress syndrome, septicemia, intracranialinfection, necrotizing enterocolitis, intracranial hemorrhage and Meconium aspiration syndrome2=0.00~1.35P=0.25~0.99.The length of stay of SGA was1611,24days, which is significantly longer thanthat of AGA1310,17,The hospitalization cost of SGA1600011400,25500yuan was much higher than that of AGA127009375,18300yuan Z=7.89P0.01. About75.85%of hospitalized neonates were cured, with19.88%conditionsimproved and0.29%died. About85.0%of hospitalized neonates were cured, with14.3%conditions improved and no death in this survy. The cure rate of SGA was lowerthan that of AGA, and the mortality of SGA was higher than that of AGA.IUGR model was successfully established.The taurine levels of fetal rat brains incontrol IUGR and taurine groups were2.399±0.134g/ml1.881±0.166g/mland2.170±0.191g/ml, respectively (F=24.828, p<0.01).Neural cell Apoptosis of the fetal rat with IUGR: In control group, there were fewexpression of TUNEL positive cells in cerebral cortex. A large amount of TUNELpositive cells were found in the cortex, hippocampal and white matter area in modelgroup, but less positive cells were identified in taurine group than model group. Theamounts of apoptotic brain cells of the three groups were (0.46±0.11)(14.76±3.42)and (6.78±1.93)%, respectively (H=429.80,(P <0.01).GDNF: There were only small amounts of GDNF positive cells in cerebral cortex incontrol group and more in model group. The amount of GDNF positive cells furtherincreased in taurine group. The amounts of GDNF positive cells in cerebral cortex ofthe three groups were93.56±6.73,120.36±6.23and139.56±5.28respectively(H=715.17, P <0.01).Caspase-3: Few caspase-3positive cells were found in cerebral cortex in control group.A large amount of positive cells were found in model group, less positive cells werefound in taurine group, still more than these of control group. The amounts of caspase-3positive cells of the three groups were7.50±2.31,151.32±24.43and37.28±11.21,respectively (F=132.54, P <0.01).PCNA:The PCNA-mRNA level of the model group was higher than that of controlgroup(P<0.05).The PCNA-mRNA level of the taurine group were further higher thanthat of the IUGR group. Few PCNA positive cells were found in cerebral in controlgroup A large amount of positive cells were found in model group(P<0.05) Theamount of GDNF positive cells further increased in taurine group(P<0.05).RhoA and ROCK2The RhoA and ROCK2-mRNA level of the model group was higher than that of control group (P<0.05) The RhoA and ROCK2-mRNA level oftaurine group was higher than that of the control group but lower than that of the modelgroup (P<0.05).Conclusion:(1)IUGR is a common clinical complication of pregnancy with an incidence of8.77%;The IUGR incidence in preterm infants (16.43%) was higher than that in full-terminfants (7.87%), and was higher in female (55.1%) than that in male (44.9%). Theresults also showes that IUGR has significantly adverse influence on fetal-neonatalhealth.(2)IUGR fetal rats brain with low levels of taurine, while antenatal taurinesupplementation can significantly incerase taurine contents in IUGR fetal rat braintissue.(3)Antenatal taurine supplementation can improve brain development of fetal rats withIUGR via following pathways: significantly alleviate neural cell apoptosis throughupregulation of GDNF and downregulation of caspase-3expression. inhibit theactivation of Rho-ROCK pathway. |
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