美金胺对缺氧缺血的脑保护及对HSP70合成的影响研究 儿科学(新生儿)专业毕业论文.docxVIP

EFFECT EFFECT OF MEMANTINE ON HSP70 SYNTHESlS AND NEUROPROTECTION AGAINST HYPOXIC．ISCHEMIA IN NEoNATAL RAT MoDELS DETAILED ABSTRACT Hypoxic。ischemia brain damage(HIBD)following perinatal asphyxia is a common problem in the neonatal period that usually causes either infant death or severe neurological sequelae later on． One of concerned focal points internationally is to explore the exact pathogenic mechanism of HIBD and to seek a safe and effect way for the treatment Of HIBD． Recent an excitotoxic theory of neuronal death induced by calcium overload has become one of the primary theories in the annotation of HIBD．Neonates usually exist a higher susceptibility for HIBD owing to their brain features physiologically and biochemically．Some cerebral regions such as cortex，striatum and hippocampus，where there is a dense distribution of NMDA receptors，are in particular easier tO induce hypoxic i schemia(HI) injury． Cerebral HSP70 gene does not normally expressed or expresses at an extremely low amount and degrades soon．However， HI can intensify both of the expression of cerebral HSP70 gene and synthesis of HSP70 specially．It is usually considered that HSP70 gene and its product，HSP70 are a sensitive maker of neuronal injury caused by HI．The determination of HSP70 gene and its products will be helpful not only to explore the pathogenic mechanism of HIBD and to estimate the severity of HIBD，but also to be an obj ective indicator for the therapeutic evaluation of neuroprotectjonal neuroprotectjonal agents． The corresponding NMDA—receptor antagonists are hence concerned and re searched based on the excitotoxic theory of the N MDA receptor．However，nO agent until nOW is confirmed as both safe and effect against cerebral HI． It was recently reported that memantine，a non—competitive antagonist at the NMDA receptor，could possess the effect of 11europrotection against HI．The high therapeutic index of the agent is due to its low—affinity binding with PCP site and its blocking a