Effects of intrauterine hypoxia on intestinal flora in newborn rats / 中国新生儿科杂志

Objective:To study the differences of intestinal flora between neonatal rats with intrauterine hypoxia and healthy neonatal rats using high-throughput sequencing technology to determine the effects of intrauterine hypoxia on neonatal intestinal flora.Methods:Intrauterine hypoxia model were established in neonatal rats. On d1 and d7 after birth, intestinal samples were collected from intrauterine hypoxic group and normal control group and assigned into INH1 group (intrauterine hypoxia d1), INH7 group (intrauterine hypoxia d7), NOR1 group (normal control d1) and NOR7 group (normal control d7). 16S rRNA sequencing were conducted using these samples and the differences in the diversity, richness and composition of the flora among the groups were compared.Results:(1) The Alpha diversity of the intestinal flora in the INH1 group was higher than the NOR1 group. Specifically, both sobs and chao indices, representing the richness of the flora, in INH1 group were significantly higher than the NOR1 group (sobs index: 114.5±35.6 vs. 50.5±21.3, chao index: 135.6±38.5 vs. 73.9±28.8)( P<0.05). Compared with the NOR7 group, the mean values of sobs, ace, chao, simpson and shannon indices in the INH7 group showed no significant differences ( P>0.05). (2) At the phylum and genus level, the dominant bacterial groups in the intrauterine hypoxia group on d1 were firmicutes and streptococcus and proteus and escherichia for the normal control group. The difference of intestinal flora between intrauterine hypoxia group and the normal control group on d7 was smaller than the difference between the two groups on d1. Compared with INH1 group, the INH7 group had increased escherichia composition and decreased streptococcus composition. Conclusions:Intrauterine hypoxia changes the initial colonization and later affects the abundance and structural composition of the intestinal flora in newborn rats.

Compound brain peptide gangiioside can improve intrauterine hypoxia-induced neonatal brain injury and promote synapse regeneration in a mouse model / 中国组织工程研究

BACKGROUND: The most current application of compound porcine cerebroside and gangiioside injection (CPCGI) focuses on the clinical therapeutic efficacy in some craniocerebral injuries and neonatal hypoxic ischemic encephalopathy, but the molecular mechanism of CPCGI involved in the recovery of nerve function is rarely reported. OBJECTIVE: To study the protective effect and mechanism of CPCGI in a neonatal mouse model of intrauterine hypoxia-induced brain injury. METHODS: Fifteen Kunming mice were randomly divided into control group, hypoxia group and treatment group. At the 14th day after pregnancy, mice in hypoxia group and treatment group were put into a 10% oxygen incubator to make the model of intrauterine hypoxia. After delivery, neonatal mice were intraperitoneally injected with CPCGI and PBS respectively, and mouse development in each group was observed after treatment. Mice in the control group were not hypoxic and treated. The expression of glial fibrillary acidic protein, Neurocan, SynDIGI and collagen IV were observed by immunofluorescence staining and western blot assay. A step-down test was used to test animal memory function. The study protocol was approved by the Animal Ethic Committee of Luohe Medical College in China. RESULTS AND CONCLUSION: Compared with the control group, the expressions of glial fibrillary acidic protein and Neurocan in the hypoxia group were significantly increased, while the expressions of SynDIGI and collagen IV were significantly decreased. The expression of SynDIGI and collagen IV in the treatment group was significantly increased than that in the hypoxia group, while the expression of glial fibrillary acidic protein and Neuroncan was significantly decreased than that in the hypoxia group. The learning and memory ability of mice in the hypoxia group was significantly decreased compared with the control group, but was significantly improved after CPCGI treatment. These results suggest that CPCGI can alleviate brain injury and improve learning and memory ability after hypoxic ischemic encephalopathy. The detailed mechanism might be related to inhibiting activation of astrocytes, down-regulating Neuroncan expression, up-regulating collagen IV expression, promoting synaptic reconstruction and reducing cerebrovascular injury.

Study on value of umbilical artery combined with fetal middle cerebral artery for detecting fetal intrauterine hypoxia / 重庆医学

Objective To study the value of umbilical artery(UA)combined with fetal middle cerebral artery(MCA)for detecting fetal intrauterine hypoxia.Methods A total of 349 pregnant women undergoing childbirth in our hospital from February 2015 and February 2016 were divided into the observation group(fetal intrauterine hypoxia group)and control group(normal fetus group)according to the existence of fetal intrauterine hypoxia.Then the systolic peak velocity and end-diastolic velocity ratio(S/D),pulse index(PI),resistance index(RI),(S/D)MCA/(S/D)UA,PIMCA/PIUA,RIMCA/RIUA of UA and MCA were compared between the two groups.The sensitivity,specific degree and Youden index of each index for diagnosing fetal hypoxia were statistically analyzed.Results The S/D,PI and RI values of UA at 28-35+6 pregnant weeks and at 36-41 pregnant weeks in the observation group were higher than those in the control group(P＜0.05),while the S/D,PI,RI value of MCA and(S/D)MCA/(S/D)UA,PIMCA/PIUA and RIMCA/RIUA values were lower than those in the control group(P＜0.01).The resistance index corresponding ratios of MCA and UA for diagnosing fetal hypoxia had the highest Youden index.Conclusion The combined use of fetal UA and MCA resistance index ratios has higher clinical value for predicting fetus intrauterine hypoxia.

Comparison of Umbilical Venous Erythropoietin Concentration Between Non-meconium Stained Neonates and Meconium Stained Neonates of Term Pregnancy / 대한주산의학회잡지

OBJECTIVE: To determine whether meconium staining can be the indicator of intrauterine hypoxia by comparing umbilical venous erythropoietin (EPO) concentration and the number of nucleated erythrocytes (NRBC), as a marker of intrauterine hypoxia, between non meconium-stained neonates and meconium-stained neonates of term pregnancy. And to determine correlation between the number of NRBC, EPO levels and interleukin-6 (IL-6), as another mediator of intrauterine hypoxia. METHODS: In 240 neonates with gestational age ranged from 37 to 41 weeks, including 231 cases of nonmeconium-stained neonates and 9 cases of meconium-stained neonates, we performed the measurement of EPO levels by RIA, the number of NRBC per 100 white blood cells (WBC) by blood smear and IL-6 by ELISA in umbilical venous blood at delivery. Statistical analysis was performed by chi-square test, Wilcoxon rank sum test, linear regression analysis using SPSS 11.0 version statistical package. RESULTS: Amniotic fluids of meconium-stained neonates had significantly greater EPO concentrations compared with that of nonmeconium-stained controls (41.3+/-13.0 vs 26.5+/-18.9 mIU/mL, p=0.001). But there were no statistical difference in the number of NRBC, IL-6 levels and hematocrit of umbilical venous blood. The EPO levels in umbilical venous blood was correlated with the number of nucleated erythrocytes (r2=7.7%, p<0.001), and IL-6 in umbilical venous blood was correlated with the number of NRBC. (r2=11.5%, p<0.001). CONCLUSION: These results suggest that meconium-stained amniotic fluid can be associated with fetal hypoxia. And the production of fetal NRBC is thought to be stimulated by EPO and IL-6, but it requires further study of other (yet to be determined) hypoxia-derived mediators.

Relationship between Oligohydrmanios and Umbilical Venous Blood Erythropoietin Levels and Nucleated Erythrocyte Counts in Appropriate and Small for Gestational Age Fetuses at Birth / 대한주산의학회잡지

OBJECTIVE: The purpose of this study is to assess the relationship between the oligohydramnios and umbilical venous blood EPO levels and nRBC counts, and to investigate the significance of oligohydramnios as intrauterine hypoxic marker in AGA and SGA fetuses. METHODS: EPO and nRBC were measured in 217 singletons with a gestational age of 32 to 42 weeks at delivery. The subjects were divided into 4 groups: group 1 (AGA with normal amniotic fluid volume, n=129), group 2 (AGA with oligohydramnios, n=15), group 3 (SGA with normal amniotic fluid volume, n=57) and group 4 (SGA with oligohydramnios, n=11). EPO levels and nRBC counts in group 2, 3 and 4 were compared to those in group 1 using Mann-Whitney U-test. Relationship between EPO and nRBC was assessed using linear regression analysis. In addition, relationship between results of umbilical venous blood gas analysis and EPO/nRBC was assessed using the same method. P-values less than 0.05 were considered statistically significant. RESULTS: EPO levels and nRBC counts in AGA with oligohydramnios (group 2) were not significantly different from those in AGA with normal amniotic fluid volume (group 1). EPO levels in SGA with normal amniotic fluid volume (group 3) were significantly higher than those in AGA with normal amniotic fluid volume (group 1). EPO levels and nRBC counts in SGA with oligohydramnios (group 4) were significantly higher than those in AGA with normal amniotic fluid volume (group 1). There was significant positive correlation between EPO and nRBC. Parameters obtained from the umbilical venous blood gas analysis were more related with nRBC than EPO. CONCLUSION: Oligohydramnios was significant intrauterine hypoxic marker in SGA fetuses. However, the results of this study suggested that the influence of oligohydramnios on antenatal fetal condition might be less severe in AGA fetuses than in SGA fetuses. Moreover, it was likely that nRBC had stronger association with pathologic hypoxia than EPO did.

Effect of brain - derived neurotrophic factor on apoptosis of embryo brain suffered from intrauterine hypoxic - ischemic injury / 实用儿科临床杂志

Objective To investigate the effect and possible signal pathway of brain - derived neurotrophic factor (BDNF) on apoptosis of rat embryo brain cells suffering from intrauterine hypoxic - ischemic injury. Methods The uterine arteries of the pregnant rats were clamped for 30 minutes in both experimental group and control group. BDNF(2 ?g) was injected into rats in experimental group while saline was injected into rats in control group through caudal veins. The samples were collected at 24, 48 and 72 hours re-spectively after artery clamping. Neuroapoptosis of different groups induced by ischemic damage was measured by TUNEL assay. The expression of extracellular signal - regulated kinase(ERK)and c - Jun - N - terminal kinase(JNK) were observed by immunohisloche-mistry.Results The number of apoptosis cells after hypoxic - ischemic injury increased progressively with time.The apoptosis cells number in experimental group were much lower in number than those of ischemic control group.The expression of ERK increased while the expression of JNK decreased in experimental group, comparing with that of the ischemic control group, with statistical signif-icance (P

Comparison of umbilical venous erythropoietin concentration between appropriate and small-for-gestational-age neonates of term pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the intrauterine hypoxic effect in term small-for-date (SGA) neonates by comparing the umbilical venous erythropoietin (EPO) concentration between appropriately-grown (AGA) and SGA neonates at delivery and to determine the variables that correlate with the umbilical venous EPO concentration by multiple regression analysis. METHODS: 183 term singleton neonates (gestational weeks > OR =37) were enrolled and divided into 136 cases of AGA (10th-90th percentile of birth weight for the gestational age) and 47 cases of SGA (< 10th percentile of birth weight for the gestational age. At each delivery, blood gas values, concentration of EPO by radioimmunoassay and the number of nucleated erythrocytes (NRBC) per 100 white blood cells in smear of umbilical venous blood were obtained. The placentas were examined microscopically for presence of pathological infarct. Statistical analysis was done by Mann-Whitney U test, x2 test, and univariate and multiple regression analysis using SPSS statistical package (version 10). RESULTS: The median umbilical venous EPO concentration, fetal hemoglobin level were significantly higher in SGA neonates than those in AGA neonates. There was no difference in number of NRBC between AGA and SGA neonates. Multiple regression analysis model with level of NRBC, presence of placental infarct and SGA provided prediction of EPO level in umbilical venous blood at delivery (regression equation: EPO=-103.94+4.75NRBC+68.07placental infarct+36.40SGA F=15.57. r2=0.47). CONCLUSION: Term SGA neonates was considered to have compensatory, not pathological intrauterine hypoxic effect by showing increased level of EPO and normal level of NRBC in umbilical venous blood at delivery, compared with thoses of AGA. In the suspected cases of SGA antenatally, measurement of NRBC level and placental pathologic examination for infarct can be informative for estimating the extent and duration of intrauterine hypoxia.

Comparison of umbilical venous erythropoietin concentration between appropriate and small-for-gestational-age neonates of term pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the intrauterine hypoxic effect in term small-for-date (SGA) neonates by comparing the umbilical venous erythropoietin (EPO) concentration between appropriately-grown (AGA) and SGA neonates at delivery and to determine the variables that correlate with the umbilical venous EPO concentration by multiple regression analysis. METHODS: 183 term singleton neonates (gestational weeks > OR =37) were enrolled and divided into 136 cases of AGA (10th-90th percentile of birth weight for the gestational age) and 47 cases of SGA (< 10th percentile of birth weight for the gestational age. At each delivery, blood gas values, concentration of EPO by radioimmunoassay and the number of nucleated erythrocytes (NRBC) per 100 white blood cells in smear of umbilical venous blood were obtained. The placentas were examined microscopically for presence of pathological infarct. Statistical analysis was done by Mann-Whitney U test, x2 test, and univariate and multiple regression analysis using SPSS statistical package (version 10). RESULTS: The median umbilical venous EPO concentration, fetal hemoglobin level were significantly higher in SGA neonates than those in AGA neonates. There was no difference in number of NRBC between AGA and SGA neonates. Multiple regression analysis model with level of NRBC, presence of placental infarct and SGA provided prediction of EPO level in umbilical venous blood at delivery (regression equation: EPO=-103.94+4.75NRBC+68.07placental infarct+36.40SGA F=15.57. r2=0.47). CONCLUSION: Term SGA neonates was considered to have compensatory, not pathological intrauterine hypoxic effect by showing increased level of EPO and normal level of NRBC in umbilical venous blood at delivery, compared with thoses of AGA. In the suspected cases of SGA antenatally, measurement of NRBC level and placental pathologic examination for infarct can be informative for estimating the extent and duration of intrauterine hypoxia.

EFFECTS OF HYPOXIA IN UTERUS ON nNOS EXPRESSION IN POSTNATAL MOUSE PARIETAL CORTEX AND THE LEARNING AND MEMORY ABILITY OF ADULT MOUSE / 解剖学报

Objective To study the effects of hypoxia in uterus on nNOS expression in postnatal mouse parietal cortex and the learning and memory ability of adult mouse. Methods The number and shape of parietal cortex neurons during postnatal development with hypotonic hypoxia in uterus were observed by Nissl staining.The expression of nNOS in parietal cortex neurons during postnatal development with hypoxia in the uterus was studied with immunohistochmistry.The ability to learn and memorize in adult mouse was observed by Morris water maze. Results Compared with the control group,the number of neurons in parietal cortex from mouse during postnatal development in hypoxic group reduced significantly(P