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Objective To obtain the change of bcl-2/bax/fas/fasL in splenic lymphoctyes with different lasting time of hypoxicischemic brain damage (HIBD). Methods The newborn rat were divided into 6 groups by the time of being HIBD model randomly, includes 1/6/12/24/48/72 hour(s) (8 for every group),and control groups were established at the same time point. The following four apoptosis related genes bcl-2/bax/fas/fasL were tested by real time PCR. Results ( 1 ) bcl-2: the mRNA expressions of HIBD groups were lower than control groups at the same time ( P<0.01 ). Eliminated the control effects, the mRNA expressions of HIBD groups were differernt by the modeling time(P ＜0.01 ). (2)bax: the mRNA expressions of HIBD groups were higher than control groups at the same time( P ＜0.01 ), and in control group the expression of 6 h was much higher than any other groups (P<0.01 ). Eliminated the control effects, the mRNA expressions of H IBD groups were different by the modeling time( P<0.01 ). (3)bcl-2/bax: the ratios of HIBD groups were lower than control groups at the same time( P ＜0.05 ), the ratios in control groups were higher than 1 ( except for 1 h); while in HIBI) groups the ratios were lower than 1; Eliminated the control effects, the ratios were different in all the groups. (4)fas: the mRNA expressions of HIBD groups were higher than control groups at the same time ( P ＜0.01 ), and both were maximum at 6 h. (5)fasL: the mRNA expressions of HIBD groups were higher than control groups in 1 h and 6 h ( P<0.01 ), while lower than control group at other time points( P<0.01 ),the expression of 24 h was the maximum of control groups and 12 h was the maximum of HIBD groups. (6)fas/fasL: the ratios of HIBD groups were higher than control groups( P ＜0.01 ) (except for 6 h), and the ratios in control groups were lower than 1 ( P<0.01 ) ( except for 6 h), and not concentrated, while in HIBD groups were higher than 1 ( except for 24 h), between 0.69 to 5.65. Conclusion Pro-apoptosis genes ( include bax/fas/fasL) were promoted by HIBD, while anti-apoptosis gene(bcl-2) was inhibited. The maximum of pro-apoptosis genes became early in HIBD. Both the pro- and anti-apoptosis genes got their maximum at 6 h and 12 h of HIBD. The apoptosis suppression was the main effects in control groups from the ratio of bcl-2/bax, which was lower than 1. The apoptosis promotion was the main effects in HIBD groups from the ratio of bcl-2/bax, which was higher than 1, especially at 12 h. Thefas/fasL effect which is the major way of lymphocytes apoptosis was strengthened in HIBD.
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Objective To investigate the different influences of pre-and/or postnatal hypoxia on the thyroid function of newborns. Methods Newborn infants of fetal hypoxia and/or birth asphyxia diagnosed and treated in pediatric department of Tianjin Medical University Genera] Hospital during last 5 years ,were assigned into intrauterine distress group (group B,n =87) ,birth asphyxia group (group C,n =36) and both of birth asphyxia and intrauterine distress group (group D,n = 75 ). Normal neonates born during the same period served as control group( group A,n =30). Blood concentrations of T3 ,T4 and TSH were detected by radioimmunoassay. Results The serum levels of T3 ,T4 and TSH in A,B,C,and D groups were (0. 86±0. 22) μg/L, (0. 62±0.21)μg/L,(0. 46±0. 19)μg/L,(0. 54±0. 19)μg/L; (125. 13±36.37)μg/L, (107.46±32.21)μg/L,(74.60±26.52)μg/L, (102.23±30.29) μg/L; (6.28±1.96) μg/L, (4.91±1.69) mIU/L, (8.66±2. 00) mIU/L, (5. 64±1.17 mIU/L). There were significant differences among the 4 groups ( P < 0. 01 ). As compared to A group,the serum T3 and T4 concentrations of B ,C and D groups were significantly decreased (P <0. 01 ,P <0. 05 ). No difference of TSH concentrations was found between A and D groups( ( P > 0. 05),but there was significant decrease in B group and significant increase in C group( P <0. 01 ). Conclusion Preand postnatal hypoxia results in decreases of T3 and T4 values,it is likely that newborns of intrauterine distress have decreased TSH, whereas those of birth asphyxia have increased TSH.
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Objective To explore the mechanism of hypoxic-ischemic brain damage(HIBD) and provide new ideas for clinical treatment of hypoxic-iscbemic encephalopathy.Methods Neonatal 7-day-old Wistar rats were randomly divided into sham-operation control group,HIBD 6 h,12 h,24 h,48 h and 72 h groups(n =6 per group).The model of HIBD was induced by unilateral carotid ligation followed by timed exposure to 8% oxygen.The expression of MMP-9 mRNA and TIMP-1 mRNA in brain tissue of neonatal rats was measured by Real-time Q-PCR method.Results (1) The ligatod brainhemisphere of HIBD groups showed obvious edema from 12 h to 48 h after hypoxia -ischemia in the neonatal rats.(2) The expression of MMP-9 mRNA was very low in the sham-operation control group,but in HIBD groups,it began to increase at 6 h,and reached a peak at 24 h,then gradually decreased,but still maintained at high level at 72 h(P＜0.01).(3) The expression of TIMP-1 mRNA was aslo very low in the sham-operation control group.But in HIBD group,it increased slightly at 6 h,12 h and 24 h,compared to the sham-operation control group,each group was statistically significant(P＜0.05),with no significant difference among the three groups(P＞0.05),then decreased at 48 h and 72 h,but with no significant difference from sham-operation control group (P＞ 0.05).(4) The ratio of MMP-9 mRNA/TIMP-1 mRNA was normal in the sham-operation control group and HIBD 6 h group,it began to increase at 12 h,and reached a peak at 48 h,then gradually decreased,but still maintained at high level at 72 h(P ＜0.01).Conclusion Hypoxia-ischemia increases the expression of MMP-9 mRNA in brain tissue of nenatal rats,and the imbalance in the expression of MMP-9 mRNA and TIMP-1 mRNA possibly is one cause of brain edema induced by HIBD.
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Objective To observe the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the expressions of caspase-3 and X-linked inhibitor of apoptosis protein (XIAP) after hypoxic-ischemic brain damage (HIBD) in neonatal rats and to investigate its neuroprotection and effective dose. Methods Sixty neonatal rats were randomly allocated to one of three groups: sham operation, saline control and PACAP groups. The PACAP group was redivided into high (10-8 mol), medium (10-9 mol) and low (10-12 mol) dose groups. An animal model of HIBD was established. Real-time fluorescent quantitative polymerase chain re-action method was used to detect the expressions of caspase-3 mRNA and XIAP mRNA on af-fected side of brain 24 hours after HIBD in neonatal rats, and spectrophotometry was used to detect the activities of caspase-3. Results Twenty-four hours after HIBD, caspase-3 mRNA expression and enzyme activity, as well as XIAP mRNA expression in the saline control group were increased significantly compared to the sham operation group (all P <0.01). Caspase-3 mRNA expression and enzyme activity in all the PACAP groups were significantly lower than those in the saline control group (all P <0.01), while XIAP mRNA expression was significantly higher than that in the saline control group (all P < 0.01 ). Conclusions PACAP may upregu-late XIAP mRNA expression, inhibit caspase-3 mRNA expression and enzyme activity. It has neuroprotective effect on HIBD in neonatal rats, and it is effective with high, medium and low doses.
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Objective To explore the protective mechanism of fructose-1, 6-disphophate on the hypoxic-ischemic brain damage of neonatal rats.Methods Seven-day-old Wistar rats were randomly divided into HIBD control group,saline-treated group, FDP-treated group. FDP-treated group was redivided into groups of high, middle and low dose.The expression of caspase-3mRNA was detected at 24h after HIBD with RT-PCR. Results There were no sifnificant differences of the caspase-3 mRNA expression among the saline-treated group, HIBD group and low dose FDP-treated group(P >0.05).The expressions of caspase-3 mRNA in the middle and high dose FDP-treated groups decreased significantly as campared to the above three groups (P < 0.05), but there was no significant difference between the two groups (P > 0.05). Conclusion The neuronal protective mechanism of FDP might be related to dewnregulate the gene expression of caspase-3 in brain tissue,and decrease the apoptosis of neuron after HIBD.
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Objective To explore the therapeutical effect of somatostatin(SST) on the damaged bowel barrier of 7-day-old SD rats with hypoxic-ischemic encephalopathy(HIE). Methods Total 7-day-old SD rats were randomly divided into untreated control group(n=6), sham-operated group(n = 6), HIE model group(n = 8) and SST-treated group(n = 8). After 6 hours of operation, abdominal aorta blood of the rats was collected to measure the level of D-lactic acid, the ileum was taken for pathological analysis and immunohistochemistry staining of SP. Results The level of D-lactic acid in HIE model group was obviously increased[(10.30 ± 1.70)mg/L], and there were significant differences compared to untreated control group, sham-operated group as well as SST-treated group respectively(P < 0.05, respectively). The cillia of ileum became widen and shorten, and the number of it decreased. At the same time, in the stratum mucosa and the neurofibrillary tangle, the expression of SP was increased (average optical density: 12.67 ± 5.46), and there were significant differences compared to untreated control group, sham-operated group as well as SST-treated group raspectively (P < 0.05,respectively).Compared with HIE model group,the level of D-lactic aeid decreased obviously[(7.35 ± 1.55) mg/L] in SST-treated group,and there were no differences compared to untreated control group and sham-operated group respectively. The intestinal villi became thinner and higher in the SST-treated group, even the number increased. Besides that, the expression of SP decreased(average optical density: 0.73 ± 0.09), and there were no differences compared to untreated control group and sham-operated group respectively. Conclusion The therapeutical effect of SST on the bowel barrier damage of 7-day-old SD rats with HIE is clear.
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Objective To study the expression of vascular endothelial growth factor(VEGF) mRNA in neonatal rats with HIBD and to explore the function of VEGF in HIBD. Methods Fourty-eight Wistar rats of 7-day-old were assigned randomly to the control or HIBD groups. The left common carotid artery of rats in HIBD group were isolated and ligated, then exposed to hypoxic environment (8%O 2) for two hours. In control group the rat left common carotid artery were isolated, but not ligated and not exposed to hypoxic environment. Animals were killed in 3 h, 12 h, 24 h and 3 d after HIBD. The expression of VEGF mRNA in hippocampus were examined by RT-PCR.Results VEGF164 was the most prominent transcript of VEGF mRNA splice variants. The expression of VEGF mRNA was present in control group, but there were no significant differences between time points ( F =0.176, P =0.911). Levels of VEGF mRNA in HIBD group were higher than that in the control group at all time points( P
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Objective To investigate the application of stable microbubble test ( SMT) and surfactant protein A ( SP-A) level in gastric aspirate in predicting neonatal respiratory distress syndrome ( RDS). Methods One hundred and ten high-risk preterm infants within 1 hour after birth, with gestational age between 24 and 36 weeks, birth weight between 1 160 g and 2 010 g were admitted in the study. The gastric secretion of 1-2 ml was collected during routine aspiration for SMT. At the same time SP-A level was measured by enzyme linked immuno sorbent assay. Results The SMT count and SP-A level in preterm infants with RDS were lower than those of infants without RDS [SMT: (5. 7?2. 4) microbubbleg/mm2( mb/ mm2) vs. (12.4?6.0) mb/mm2, t = 8. 355,P
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Objective To explore the expression and effect of interleukin(IL)-18 after hypoxic-ischemic brain damage(HIBD) in neonatal rats. Methods The HIBD model of seven-day-old Wistar rats was established. The mRNA and protein for IL-18 in cerebral cortex of control group, HIBD3 h, 8 h, 24 h, 3 d, 6 d and 14 d group were analyzed by RT-PCR and immunohistochemistry respectively, at the same time histological changes were observed. Results The expression of IL-18 mRNA and protein was low in control group[mRNA: 0.321 8?0.046 6; protein: (6.033? 1.019)cells/field]. After HIBD, the level of mRNA/protein for IL-18 in ischemic cortex increased progressively at 24 h to 6 d [mRNA: 24 h: 0.582 3?0.074 0, 3 d:0.697 6 ?0.107 3, 6 d: 0.911 0?0.064 7; protein: 24 h: (19.133?2.094)cells/field, 3 d: (28.900 ?1.589) cells/field, 6 d: (52.883?3.203)cells/field; P
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Objective To investigate the protective mechanism of 7-nitro indazole (7-NI) in neonatal rats with hypoxic-ischemic brain damage. Methods Seventy-two Wistar rats of 7-day-old were randomly divided into the sham-operation、HIBD and 7-NI treated group. The HIBD models were established in 7-NI treated and HIBD groups.7-NI (100 mg/kg) or peanut oil (10 ml/kg) was injected intraperitoneally 0.5 h before hypoxia in 7-NI treated group or HIBD group. NOS,NO,SOD and MDA were examined at different time (1 h、2 h、6 h、8 h). Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL) method was used to detect neuronal apoptosis. Results NOS and NO level of HIBD group at different time were significantly higher than that of the sham-operation group [NOS:1 h (3.345?0.367)U/mg, 8 h (4.469?0.275) U/mg vs (1.555?0.223) U/mg; NO: 1 h (2.419?0.254) ?mol/g, 8 h (3.556?0.309) ?mol/g vs (0.749?0.135) ?mol/g, P