Effects On The Change Of Neuroglobin With Cerebral Hypoxia-ischemia Caused By Hypoxia Preconditioning On Neonatal Rats

Hypoxic-ischemic encephalopathy (hypoxic-ischemic brain damage,HIBD) is one of the major diseases in neonatal period,It is resulted from birth asphyxia and caused acute mortality and chronic neurological disability in newborn. The diagnosis and treatment about it have still more difficulties. Despite extensive research are the main reason for HIBD,but pathological mechanisms caused by HIE not fully understood. While the therapy efficiency of present methods are not very ideal. At present not many effective therapeutic interventions are available for clinical use. Currently experimental protective interventions for HIBD including glutamate receptor antagonists,NO synthesis inhibit- tors,calcium channel blockers,oxygen free agent scavenger and inhibitors. But the result was unsatisfactary,So it is very necessary to look for an effective means of brain protection.Low volume fraction of oxygen (hypoxic) preconditioning (hypoxic preconditionin-g,HP) refers to one or more short-term mild hypoxia and trigger the body's inherent protective function,defense and protect the subsequent incidents of serious ischemic/ hypoxic. HP has become one of the important way at the anti-ischemic/hypoxic study. It has been confirmed to have a protective effect on the brain and other organs(for exemp les:heart,retina,liver and kidney).At present the results of some separate research found that hypoxic preconditioning have come to close with hypoxia-inducible factor, NO,adenosine,excitatory amino acids,free radicals and some cytokines.Neuroglobin(Neuroglobin,Ngb) which is important globulinare similar to hemoglobin and myoglobin. Ngb binds oxygen reversibly and plays an important role in oxygen homeostasis of neural tissues. Their common characteristics is carryed O₂ to the respiratory chain of aerobic metabolism. Ngb which lie in human and mammalian is expressed of a variety of organizations,but mainly in the brain and retina. It can reversibly combine with oxygen and has a high affinity with oxygen specificity the metabolism of brain tissue. It play an very important role at oxygen uptake,transport and use of physiological processes in the nervous system. Our experiment discuss changes of neuroglobin in neonatal rats with cerebral hypoxia-ischemia after hypoxia preconditioning.Objective To observe the effects of hypoxia preconditioning (HP) on the change of neuroglobin (Ngb) in neonatal rats with cerebral hypoxia-ischemia.Methods One hundred and twenty the 7-day-old wistar rats were randomly divided into 3 groups:sham operatetion group (n=20),hypoxic-ischemic brain damage (HIBD) group(n=50) and hypoxic-ischemic brain damage after hypoxia preconditioning (HP)(n=50).The rats in HIBD and HIBD after HP were further divided into 5 subgroups respectively based on 1,5,15,30,60minutes after model was set up. The neonatal rats of carotid artery ligation was used as the research model. Preconditioning was performed 24hours before hypoxic-ischemic (HIE) by placing rats in the hypoxic chamber for 3hours.The brain tissues were taken from the rats at 1,5,15,30and60min respectively after the models were made in HIBD group and HIBD after HPC group. The expressions of Ngb of brain tissues were studied at 1,5,15,30and60min after HIBD using immunohistochemistry and quantitative reverse transcription polymerase chain reaction(RT-PCR) respectively.Result RT-PCR analysis showed that the relative expression of Ngb in brain tissue at 1,5min (A: 1.59±0.20,1.98±0.22) in HIBD group were significantly higher than those in the sham-operated group (A: 1.52±0.25) (Pall<0.05) respectively,but there was no significant difference at 15min,30min and 60min between HIBD group (A: 1.55±0.28,1.52±0.25,1.51±0.24) and sham-operated group(Pall>0.05),and there were no significant difference between the HP group(A: 1.60±0.26,1.99±0.30,1.56±0.23,1.53±0.20,1.53±0.27) and the HIBD group(Pall>0.05).The result of immunohistochemistry showed that there was no significant difference between the level of Ngb in HIBD after HP group(195.00±11.26,202.41±12.2,182.60±15.72,178.22±14.37,164.86±28.99) and HIBD group(195.59±11.59,201.40±13.61,178.09±18.92,173.75±14.3,163.45±18.66) (Pall>0.05).Conclusion HPC has protective effect on neonatal rats with cerebral hypoxia-ischemia,but Ngb does not have obvious protective effect on HIE.