| The clinical and fundamental studies on cerebral ischemia diseases are always the hot spot. Although the great progress has been made in the aspects of mechanisms, medicine protection,gene treatment, the studies in some fields are not still clear,especially in the aspect of prevention and treatment and the endogenous cerebral protective mechanisms. Now it is believed that when exposed to a brief sublethal ischemia /hypoxia which can be regarded as a injurious stress response, most living organisms can mobilize the self-protective mechanisms to protect brain from the subsequent lethal ischemia, that is the induction of ischemia tolerance. Some progresses have been made in the studies of ischemia tolerance, but the underlying mechanism of neural protection is still not fully undersood. The methods and duration still need to explore.Various mechanism are reported on the neural protective effect of ischemia tolerance. Transient hypoxia can target complex gene expression in the brain, which includes the protein kinase signal pathways,immediate-early genes (IEG),growth factors, oxidative stress enzyme and so on.So it is not strange that the induction of ischemia tolerance is controled by various mechanisms which act on ischemia in different time and spatial patterns.It has been attach importance to the role ofHIF-1αand it's target gene on cerebral ischemia and hypoxia preconditioning.In our studies, the expression changes of HIF-1αand it's target gene EPO,GLUT-1 were observed after permenent focal ischemia and hypoxia preconditioning to further explore the protective mechanisms of hyoixa preconditioning in the brian and to provide the direction on the clinic practice.PMCAO model in rats was induced using the filament method and the model of hypoxia preconditioning was also established. The evaluation of this model and the investigation of neural protecive effect were performed on neurological deficits, infarct volume deternmination, histopathology changes and GFAP immunohistochemical stain .The expression of HIF-1αand it's target gene EPO,GLUT-1 was examined by immunohistochemical method and in stiu hybridization and the neural protective mechanism of hypoxia preconditioning was studied further more.Part 1 Evaluation of animal model and the investigation of neural protective effect of hypoxia preconditioning. PMCAO was induced using filament method in this study with a modification on the tip of the nylon suture .Different time hypoxia preconditioning was performed 24h before PMCAO.Praxiology changes and neurologic deficit were examined for the evaluation on utility of this animal model.Infartion volume was calculated by TTC staining.HE staining and GFAP immunohistochemical staining were used to investigate the histopathology changes. It was showed that the PMCAO medel in our experiment was resemble to the clinic symptoms and histopathology change of cerebral ischemia diseases. Normobaric hypoxia preconditioning (8%O2, 92%N2for1h, 3h, 5h duration), performed 24 hours before ischemia ,can produce protective effect on subsequent PMCAO by reducing infart volume by approximatedly 31%, decreasing the neurologic deficit when compared with controls. The histopathological injuries of rats were lightened by HE and GFAP staining. It is proved that hypoxia preconditioning can induce the ischemia tolerance and has protective effect to the brain.The model was useful for its stability and essy to be duplicated and it can regarded as a ideal model for studing hypoxia preconditioning. Part 2: It is knowed that hypoxia preconditioning can induce ischemia tolerance and has protective effect on the brain,but the underlying mechanism about it is not elucidated till now.HIF-1 and its target gene EPO,GLUT-1 are all the oxygen sensitive genes .It has not detail report about the expression changes of HIF-1 and its target gene EPO, GLUT-1 after permenent focal ischemia and hypoxia preconditioning in rats domestic. The expression of HIF-1 and its target gene EPO, GLUT-1 was examined by immunohistochemical staining...
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