The Protective Effect Of Ngb Expression Induced By Hemin On Focal Ischemic Brain Tissue Of Rats

Backgroud and objective:Cerebral vascular disease (CVD) is a sort of critical disease characterized as high incidence rate, high disability rate and high mortality, which seriously threatens humankind's health. In China, more people die from CVD than other two diseases as cardiac disease and cancer. About 60% to 80% of all CVD patients is ischemic cerebral vascular disease (ICVD). As the population of our society becoming aged, the incidence rate of ICVD is getting higher and higher. But how to decrease the disability rate and mortality effectively is still a key problem of treating ischemic stroke.The pathophysiological change of ICVD is focal ischemia and hypoxia of brain tissue,which induce a series of pathologic metabolism or signal transduction such as overfull-produced free radicals and waterfall-like reactions, Ca2+ overloading in neuronal cells, toxicity of excitatory amino acid, acid toxicity and apoptosis.The key therapy of ICVD is to resume blood flow of ischemic brain tissue timely. However, the update hot field of research is to extend the therapy time window to resume focal brain blood flow. One prominent feature of cellular adaptation to hypoxia or ischemia is the increased expression of hypoxia-inducible proteins, such as hypoxia-inducible factor (HIF-1), erythropoietin (EPO), vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1). These proteins are likely to exert their neuroprotective effects through diverse mechanisms, but their hypoxia-responsiveness depends ultimately on oxygen-binding proteins that can response to hypoxia and trigger appropriate cellular adaptations. Neuroglobin (Ngb) is a recently discovered globin that is expressed specially in vertebrate brain and can reversibly bind oxygen. Sun Y reported that Ngb was up-regulated in cultured cortical neurons deprived of oxygen, and an Ngb antisense oligodeoxynucleotide (ODN) to inhibit Ngb mRNA increased hypoxic neuronal injury. They also reported that in rats, intracerebroventricular administration of a Ngb-expressing adeno-associated virus (AAV) vector reduced infarct size to 50% campared with...