Morphine preconditioning-induced tolerance to cerebral anoxia resulting molecular mechanism of.doc

 PAGE \* MERGEFORMAT 5 Morphine preconditioning-induced tolerance to cerebral anoxia resulting molecular mechanism of Pretreatment on morphine-induced tolerance to cerebral anoxia resulting mechanism of research is currently mainly in the animal’s overall and cell levels, mainly related to the following aspects of the mechanism. 1. Cerebral hypoxia (ischemia) caused by the molecular mechanism of nerve cell death Neuronal hypoxic neuronal death mainly in the following several ways: 1. Excitatory amino acid-induced neuronal death Glutamate is the central nervous system, the major excitatory neurotransmitter and its receptors can be divided into ionic and Metabolizers. Hypoxia / ischemia can induce a sharp increase in extracellular glutamate levels, NMDA receptor, a large number of open, so that Ca2, Na, Zn2, Cl-influx, K outflow, causing intracellular calcium overload, membrane depolarization by damaged cells, edema, eventually leading to loss of membrane function, post-synaptic nerve cell death. 2. Receptor-mediated neuronal death Fas receptor (CD95/APO-1) belongs to tumor necrosis factor receptor (TNFR) super family, is a membrane translocation of apoptosis receptor protein precursors, can trigger apoptosis processes leading to cell death. In the central nervous system, Fas receptor expression level is usually very low. When stimulated by stress signals, such as hypoxia, Fas receptor and ligand (Fas Ligand) were increased. In tumor necrosis factor superfamily, TNF-α over-expression may be mediated through the following means neuronal damage: 1) TNF-α direct neuronal toxicity can be induced neuronal apoptosis; 2) TNF-α can enhance glutamyl acid and AMPA receptor-mediated neuronal excitability injury; 3) can silence neuronal survival signal (silencing of the survival signals, SOSS); 4) TNF-α is still a strong pre-inflammatory cytokines. 2. Peroxidation Hypoxia / reperfusion can lead to