| Objective　With the old population increasing in the world, the incidence rate of senile dementia is increasing gradually. More than half of the senile dementia is alzheimer's disease, because it's pathogenesis is very complex and it's etiology is unknown, there hasn't a drug which can treat it thoroughly or reverse it's course for the time.Since the excitotoxicity was suggested, some researchers paid close attention to the relation of excitotoxicity and neurodegeneration. Many experiments confirmed that the pathogenesis of AD was related to excitotoxicity. And it was presumed that excitotoxicity was the primary pathogenesis of AD. Studies further indicated that excitotoxicity resulted the neurodegeneration through two steps. Firstly, it resulted the excessivly inflow of Na+, which damage the brain reversibly, then it resulted in excessively inflow of Ca2+, which resulted in a series of damage. So blocking of the inflow of Ca2+, so as to diminished the overload of Ca2+ and their related damage is hope to relieve the neurodegeneration . Tetrandrine is a bisbenzylisiquinoline alkaloid, Electrophysiological and clinical experiments have manifested that Tet was a Ca2+ antagonist. It has been confirmed that it had pharmacological effects on anti-arhythmia anti-hypertention, anti-myocardial ischemia, anti-flamation, and so on. Our previous experiments and other's studies indicated that Tet couldblock the accumulation of rat brain cells. It could protect the rat brain from cerebral ischemia-recirculation. But there hasn't study about it's protection from the lesion of hippocampus neurons induced by excitotoxicity .This topic is aim to study whether Tet can protect the hippocampus neurons from quinolinic acid in vivo and in vitro and it's effect factors related, so as to find a new potent agent for senile dementia and other neurodegeneration disease.Method In vitro: primary hippocampus neurons were cultured using embryo rat brains, the MTT and the activity of LDH were assayed and the pathology was observed, so as to study the protection of Tet from excitotoxicity induced by quinolinic acid(QA). In vivo: Animal models were made by injecting QA into both CA1 districts of hippocampuses with microinjector, then their praxiology and pathology were observed to study the protection effect of Tet. Fortheremore, the content of MDA, the activity of NOS and ATP enzymy were assaied and the apoptosis were observed so as to study the protection factors related to Tet.Results and conclusions:(1) Tet(10-6 mol/L,10-7mol/L)could incease the survival rate of hippocampus neurons in vitro damaged by QA,diminished their release of LDH and improved their pathological morphology,these effects were significantly different from those of model, which indicated that Tet(10-6 mol/L,10-7mol/L)could protect remarkably the primary Hippocampus cells from the damage of excitotoxicity.Tet(10mg/kg,15mg/kg)could ameliorate the ability of spatial learning and conditional learning of dementia models,improved pathological morphology of their brains ,and the differences were significant compared to model, which indicated that Tet(10mg/kg,(2) 15mg/kg)could protecte the neurons of dementia models from the excitotoxicity.(3) The content of MDA, the activity of NOS and their rate of apoptosis of primary Hippocampus neurons cocultured with QA were increased,but their activity of Na+-Ka+-ATP enzyme and Ca2+-Mg2+-ATP enzyme were decreased .Tet(10-6 mol/L,10-7mol/L)could decrease the content of MDA, the activity of NOS,increased the activity of Na+-Ka+-ATP enzyme and Ca2+-Mg2+-ATP enzyme, these differences were significant compared to those of models,and could relieve the apoptosis, so we presumed that the protection of Tet (10-6 mol/L,10-7mol/L)from excitotoxicity is related with these factors.
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