| Objective Histological chorioamnionitis was the main form of intrauterine infection.Parturients had no clinical symptoms and were easy to miss diagnosis,resulting in a high incidence of adverse neurological outcomes in premature infants.Brain injury was the pathological basis of neurodevelopmental abnormality in premature infants.Therefore,in this study,premature infants with gestational age less than 34 weeks were taken as the research object to explore the effect of HCA on brain injury of premature infants,and to strengthen obstetricians and pediatricians'in-depth understanding of HCA,so as to reduce neurological complications and improve their long-term quality of life.Methods(1)Research object:To collect the clinical data of premature infants and their mothers who were born in the obstetrics department of Qingdao Women's and Children's Hospital from January 2019 to June 2020 and were admitted to the neonatal intensive care unit of the hospital whose gestational age was less than 34 weeks and whose mothers completed placental pathological examination.and the outpatient follow-up data of some premature infants.Moreover,excluding premature infants with hypoglycemic encephalopathy,bilirubin encephalopathy and central nervous system infection,fatal congenital malformations,genetic metabolic system diseases or chromosome abnormalities,mothers suffering from clinical chorioamnionitis,death/incomplete data.(2)Group:According to the degree of placental inflammatory cell infiltration,the preterm infants were divided into HCA group and non-HCA group.The occurrence and clinical characteristics of brain injury in the two groups were observed.In addition,according to the different stages of HCA,the premature infants in HCA group were divided into early HCA group and middle and late HCA group,and the relationship between the severity of HCA and the risk of brain injury in premature infants was further analyzed.Results(1)During the study period,327 premature infants with gestational age less than 34 weeks were treated,and 24 cases of clinical CA,central nervous system infection,genetic metabolic diseases,death,giving up treatment and incomplete data were excluded.A total of 303 eligible cases were included,accounting for 61.40%of males(186/303)and 38.60%of females(117/303).The average gestational age was 31.71(30.00,32.86)weeks,and the average birth weight was 1.71?0.39kg.(2)The overall incidence of brain injury was 18.15%(55/303).There was 188 cases in HCA,the incidence of brain injury in HCA group was 22.87%(43/188),the incidence of brain injury in the middle and late HCA group was higher than that in the early HCA group[31.25%vs 14.10%],and the difference was statistically significant.There was 115 cases in non-HCA,the incidence of brain injury in non-HCA group was 10.43%(12/115).The incidence of brain injury in HCA group was significantly higher than that in non-HCA group(P<0.05).(3)The incidence of white matter injury in HCA group was 14.89%(28/188),the incidence of intracranial hemorrhage was 1.60%(3/188)and the incidence of both was 6.38%(12/188).The incidence of white matter injury in non-HCA group was 8.70%(10/115),and the incidence of intracranial hemorrhage was 1.74%(2/115).(4)The one minute Apgar score of premature infants in HCA group was lower than that in non-HCA group[8.00(8.00,9.00)vs 10.00(9.00,10.00)],and the difference was significant(P<0.05).However,there was no significant difference in gestational age,sex,birth weight,birth length,birth head circumference,intrauterine distress and five minute Apgar score between the two groups(P>0.05).(5)There was no significant difference in age,cesarean section,gestational diabetes mellitus,gestational hypertension,placental abruption and prenatal glucocorticoid utilization between the two groups(P>0.05).(6)There was no significant difference in PH,Pa CO2,HCO3-,lactate value,invasive mechanical ventilation and non-invasive mechanical ventilation between the two groups in arterial blood gas analysis at one hour after birth.(7)The incidences of postnatal pneumonia and BPD in HCA group were significantly higher than those in non-HCA group,but there was no significant difference in the incidence of RDS,respiratory failure,NEC and PDA between the two groups.(8)According to the results of placental inflammatory infiltration,32 premature infants with brain injury were divided into non-HCA group,early HCA group and middle and late HCA group according to the results of placental inflammatory infiltration.It was found that MDI and PDI in the middle and late HCA group were lower than those in the non-HCA group at the corrected age of 6 months,and the difference was significant(P<0.05).With the increase of HCA severity at other time points,the values of MDI and PDI decreased to some extent,but there was no significant difference(P>0.05).Conclusion(1)HCA exposure increased the risk of brain injury in premature infants with gestational age less than 34 weeks,and with the increase of the severity of HCA,the incidence of brain injury in premature infants gradually increased.(2)Severe HCA has adverse effects on short-term intellectual and motor development of premature infants with brain injury.Objective Just as,it has been confirmed in the first part of this paper that HCA exposure was closely related to the occurrence of brain injury in premature infants,but the specific mechanism of brain injury was not fully understood.Therefore,in this part,the animal model of intrauterine infection was established by lipopolysaccharide to explore the changes of the expression of myelin basic protein and glial fibrillary acidic protein in the brain tissue of neonatal rats exposed to HCA,and the protective effect of glibenclamide on brain injury in HCA neonatal rats.Methods 21 Sprague-Dawley pregnant mice were randomly divided into NS group,LPS group and GLB group.The intrauterine infection model was established by intraperitoneal injection of LPS(0.5mg/kg)on the 18th day of pregnancy in LPS group and GLB group,the same dose of sterilized normal saline was injected intraperitoneally in NS group at the same time,glibenclamide(1mg/kg)was infused into the stomach of pregnant rats in GLB group after LPS 12h injection for 3 days,and the same amount of normal saline and dimethyl sulfoxide solution were infused into the stomach of pregnant rats in LPS group and NS group at the same time.After the third intragastric administration for 12 hours,one pregnant rat was randomly selected after anesthesia and the placenta was taken by laparotomy for histopathological examination.The degree of intrauterine infection and the natural delivery of the remaining pregnant rats were observed,and the number of death and the number,body weight and bood sugar of live born rats were recorded.The newborn rats in each group were randomly divided into 4 groups.The brain tissues were taken at D1,D7,D14 and D21,respectively,and the brain histopathology was examined.The expression of MBP in oligodendrocytes and GFAP in astrocytes was detected by immunohistochemical method to evaluate the degree of brain injury induced by HCA and the protective effect of glibenclamide.Results(1)General situation :After corresponding treatment,all pregnant mice in each group were able to eat and move normally.63 newborn rats were born in NS group,62 in LPS group and 65 in GLB group.Except for 3 cases of stillbirth in LPS group,there were no abortion and preterm delivery,and the gestational age of delivery was 21-22 days.There was no hypoglycemia in pregnant and newborn rats.(2)Placental pathological examination :The placental structure of pregnant rats in LPS group was disordered and a large number of inflammatory cells were diffused in the villous space,while the placental structure in GLB group was irregular,the blood supply was more abundant than that in LPS group,and some inflammatory cells were infiltrated.In LPS group,the arrangement of brain neurons was irregular,local edema,and the number of glial cells increased in varying degrees.The microscopic morphology of brain tissue in GLB group was slightly better than that in LPS group,but glial cells could still be seen.(3)Pathological examination of brain tissue of newborn rats: In NS group,the brain tissue of newborn rats was evenly stained,the arrangement of all kinds of cells was regular,and the number of neurons was abundant.The arrangement of neurons in the brain tissue of LPS group was irregular and loose,the number of neurons decreased in varying degrees,and the number of glial cells increased significantly in GLB group,while the brain tissue of neonatal rats in GLB group was slightly better than that in infected group,but the number of glial cells was still increased.(4)Body weight and brain weight of newborn rats in each group :On the first day after birth,the body weight of newborn mice in the LPS group was significantly lower than that in the NS group(P<0.017).There was no significant difference in body weight among the other groups at the same time(P>0.017).There was no significant difference in brain weight among the three groups(P>0.05).(5)MBP expression detection :There was no MBP expression in the brain tissue of newborn rats in all groups on the first day after birth.On the 7th day after birth,the positive expression of MBP in LPS group and GLB group was lower than that in NS group(0.296±0.065vs0.384±0.072,0.319v0.046vs0.384±0.072,P<0.017),but there was no significant difference in MBP expression between LPS group and GLB group(0.296±0.065vs0.319v0.046,P>0.017).Obvious brown granulation was observed on the 14th day after birth.The positive expression of MBP in LPS group and GLB group was lower than that in NS group(0.366±0.046vs0.460±0.041,0.414±0.034vs0.460±0.041,P<0.017),and the positive expression of MBP in LPS group was lower than that in GLB group(0.366±0.046vs0.414±0.034,P<0.017).A large amount of brown granule deposition was seen in the brain tissue on the 21 st day after birth.The positive expression of MBP in LPS group and GLB group was lower than that in NS group(0.409±0.034vs0.502±0.045,0.453v0.037 vs0.502v0.045,P<0.017),and the expression in LPS group was lower than that in GLB group(0.409v0.034vs0.453±0.037,P<0.017).(6)GFAP expression detection :A very small number of brown granules were found in the brain tissue of newborn rats on the first day after birth.The expression of GFAP on the 7th day after birth in LPS group was higher than that in NS group and GLB group(0.456±0.033vs0.313±0.064,0.456±0.033vs0.407±0.040,P<0.017),and the expression of GFAP in GLB group was higher than that in NS group(0.407±0.040vs0.313±0.064,P<0.017).On the 14th and 21st day after birth,the calmness of brown granules in brain tissue became more and more obvious.The expression of GFAP in LPS group and GLB group was higher than that in NS group(P<0.017)The expression of GFAP in LPS group was higher than that in GLB group(P<0.017).Conclusion(1)In neonatal mice exposed to HCA,the expression of MBP in oligodendrocytes decreased and the expression of GFAP in astrocytes increased.(2)Administration of glibenclamide during pregnancy could reduce the decrease of MBP of oligodendrocytes and the increase of GFAP of astrocytes in neonatal rats with HCA to some extent,which played a protective role in brain injury of neonatal rats. |
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