Neuro-protective function of cytoglobin on neonatal rats with hypoxic-ischemic brain damage / 中华围产医学杂志

ABSTRACT

Objective To investigate the protective function of cytoglobin (CYGB) on neurodevelopment of the neonatal rats with hypoxic-ischemic brain damage (HIBD).Methods Healthy seven day old Sprague-Dawlay rats were randomly divided into sham operated group,HIBD group,HIBD+Hemin group and HIBD+zinc protoporphyrin (ZnPP) group.The rats of HIBD,HIBD+Heminand HIBD+ZnPPgroup were given normal saline (0.5 ml),Hemin (50 mg/kg) and ZnPP (50 mg/kg) intraperitoneally respectively,and 12 hours later the left carotid arteries of these rats were ligated and cut off,then hypoxic treated for 2 hours to establish the HIBD models.At 0,24,48 h after HIBD models were established,the expressions of CYGB in the cerebral cortex and hippocampus were observed by immunohistochemistry analysis.At 48 h after HIBD,histopathological changes of brain were observed after HE staining.At 72 h after HIBD,the water content of the brain was observed.At 28 days after HIBD,long term study memory outcome was assessed by Morris water maze.Analysis of variance and Bonferroni test were applied as statistical methods.Results (1)The expression of CYGB in brain(expressed by average gray value which negatively correlated with protein levels)At 0 h,the average gray value of CYGB in the cerebral cortex in HIBD+ Hemin and HIBD group were 166.7±5.1 and 207.1±5.1,which were lower than that in sham operated group (232.3±3.4); but in HIBD+ZnPP group,it was higher (234.9±4.5)(P＜0.05).The average gray value of CYGB was decreased with the extension of hypoxic-ischemic time.At 48 h,the average gray value of CYGB was the lowest in HIBD+Hemin group (126.0± 2.6),followed by HIBD group (150.9±4.5) and HIBD+ZnPP group (163.7±6.3),and the highest was in sham operated group (232.1±5.8)(all P＜0.01).(2) Histopathologic changes of the brainAt 48 h,typical cerebral infarction and hemorrhage were seen in HIBD,HIBD+Hemin and HIBD+ZnPP group,but those were less severe in HIBD + Hemin group than in HIBD + ZnPP group.(3) The water content of the brainAt 72 h,the water content of the left brain in HIBD and HIBD+ZnPP group was (86.5±0.4)％ and (87.3±0.3)％,which was higher than that in right brain [(85.6±0.2)％ and (85.9±0.2)％] (t 12.57 and 11.32,P＜0.01,respectively).(4)Function of the hippocampusMorris water-maze showed that the longest average escape latency in HIBD+ZnPP group [(76.7±29.8) s],followed by HIBD group [(71.0±30.5) s],HIBD+ Hemin group [(46.7±34.0) s],and sham operated group [(38.3±30.3) s] (all P＜0.01).(5) Long-term histopathologic changes of the brainAt 34 d,brain atrophy rate was the highest in HIBD+ZnPP group [(34.07± 6.75) ％],and then in HIBD group [(29.73± 6.53) ％] and HIBD+ Hemin group [(18.33±4.52)％],which were all higher than that in the sham operated group [(1.55±1.32)％](all P＜0.01).HE staining showed that the hippocampal stratum pgramidale was getting thinner and a large number of neurons was lost in HIBD and HIBD+ ZnPP group,but only a small amout of neurons was lost in HIBD+ Hemin group.Conclusions Increased expression of CYGB in HIBD brain could mitigate the short term and long term pathological injury,and protect the long-term study memory function of the hippocampus.