| Background and objectivesAnoxia is the pathological state of low ventilation in tissue and cell,which is caused by the decrease of oxygen partial pressure or oxygen content in the circulation of blood by various reasons. In all organs of the body, the central nervous system is the most sensitive to the anoxia, which causes brain cells edema, degeneration and necrosis easily, even causes nerve systemic diseases.The common diseases in pediatric such as neonatal asphyxia of newborn and newborns hypoxic-ischemic encephalopathy (HIE) cause the children convulsions,the movement out of coordination or obstacles,hypophrenia and impaired ability of learning and memory, seriously cause cerebral palsy and even death. All that bring about heavy pressure and economic burden to the family and society.Energy metabolization obstacle is the earliest pathological physiology change after anoxia in the brain,then produces a series of "waterfall" responses such as increase of the oxygen radical, excessive influx of calcium, and so on, corresponding causes increase of the nitric oxide(NO) and Calmodulin (CaM).These responses can cause degeneration and necrosis for nerve cells. As the important factor of oxygen adjustment, at present hypoxia-inducible factor1alpha (HIF-1a) has been widely studied and used in oxygen deficiency of the brain damage by adjusting the expression of the target genes to play the role of the protection of neurons.Phosphocreatine is the high-energy phosphate compound which is composed of phosphoric acid and creatine,and it is the temporarily stored form of high-energy phosphate. In the molecules of phosphocreatine, it has the nitrogen-phosphorus bonds which can release the high energy after hydrolyzation,consequently,the high energy conversion to the cells through the ADP-ATP pathway, not just can be an energy buffer, but can be used as a intracellular energy carrier. At present, as a high effective and low toxic myocardial protection medicine, exogenous creatine phosphate sodium (PCr) has be widely used in treating viral myocarditis, cardiac failure and so on,which has good curative effect, and as one of the additional constituent for cardioplegic solution in heart surgery,it has been collected by Martindale:The Extra Pharmacopoeia. In recent years studies have showed that PCr has the function of protection, restoration neurons, and can decrease the brain injury of newborns hypoxic-ischemic encephalopathy, cerebral infarction,and so on. But the corresponding animal laboratory data reports are less when influence some factors change, can PCr repair brain damage or inhibit brain cells degeneration or necrosis? The aim of this topic is that during the brain injury by anoxia, preliminarily study the change of NO and CaM content, the expression of HIF-1a by means of PCr intervention, and provided the support of laboratory for the clinical application of this drug.Materials and methods1Animals and groupsA total of75young rats were randomly divided into three groups, creatine phosphate sodium treated group (PCr group), normal saline model group (NS group) and normal control group,25for each group.The rats of PCr group and NS group were established anoxia model, the normal control group was not treated.2drug applicationThe rats of PCr group were injected intraperitoneally with PCr on the0.5h before anoxia, and after anoxia immediate,24h,48h, by the dose of1.4mg/g, and in the same time, equal NS were injected respectively. Nothing was given the normal control group.3Specimens CollectionOn anoxia6h,each group took10young rats respectively which were taken in the brain and then were taken half of the brain tissue putting in the paraformaldehyde to make the pathological section; the other half of brain tissue was putted in the-80℃refrigerator to detect the relative content of HIF-la mRNA expression; on the last time of intraperitoneally injecting,each group took15young rats respectively which were taken in the brain and weighed, then putted in the-80℃refrigerator to detect the content of NO and CaM.4Statistical analysisTo analyze all the data by SPSS17.0statistical software.Standard tolerance time used T test of independent sample. Comparison among groups of NO,CaM content and the relative content of HIF-1a expression used One-way ANOVA. LSD-^was used for multiple comparison. The difference was statistically significant when P <0.05.Results1Compared with NS group (7.15±0.90), the standard tolerance time of PCr group(7.97±0.75) prolonged significantly.2Pathological changes:Compared with NS group, neural cell destruction of PCr group reduced, edema, necrosis eased significantly, and less of inflammatory cell was infiltrated.3The NO content of PCr group[(0.73±0.13) umol/g] was a little bit higher (P<0.05) than that of normal control group[(0.55±0.07) umol/g],but lower (P<0.05) than that of NS group[(0.86±0.17) umol/g].4The CaM content of PCr group[(41.19±1.13) ng/L] was a little bit higher (P<0.05) than normal control group[(39.56±0.86) ng/L], but lower (P<0.05) than model group[(42.04±0.76) ng/L].5HIF-1a mRNA had hardly expression of normal control group (0.04±0.01), but the expression of NS group (1.09±0.01) increased, and PCr group (1.00±0.02) increased much more.Conclusion PCr may have neural protection by means of prolonging standard tolerance time, decreasing the CaM and NO content and increasing the expression of HIF-1a mRNA during brain injury by anoxia. |
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