| OBJECTIVE:In 1971, Olney and his associates discovered that excited amino acids (EAAs) , such as Glutamic acid (Glu), could arose cell death of centrum neural system, and for the first time they imported excitotoxin. In recent ten years, many scholars have deemed that nervetoxin or excitotoxin of excessive Glu and its analogs are realated to some nerve system diseases, such as brain trauma, Cerebral ischemia, Cerebral anoxia, Epilepsy, Parkinson disease, Huntington chorea, Alzheimer's disease and et al. Experiment studies have approved that these nerve system diseases are likely to have respect to the dysfunction of the Glu neurons in CNS. Excitotoxin damnification is related to the 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 . Cinnarizine(Cin) is a calcium channel antagonist of piperazin. Its feature is that it is only block the entad overfull Ca2+ pathologically, and have nothing to do with the entad Ca2+ physiologically. That is to say, it can block the entad Ca2+ selectedly, and to prevent the pathological leision brings by calcium overload introcell. For its inhibition to the vasoactives, such as the histamin, epinephrine, dopamine angiotensin, et al, it can ameliorate the cycle of brain and coronary sclerosis in clinic. Studies further indicated the Cin can block the enlargement of the content of introcell Ca2+ in the brain of rats, and protect the cerebral cortex neuron which damnified by neurotoxin. And it has been also confirmed that in vivo, Cin has the transparent protection to the lesion of cerebral ischemia. But there hasn't study about its protection from the leison of hippocampus neurons induced by excitotoxicity.This topic is aim to study whether Cin can protect the hippocampus neurons from quinolinic acid in vitro and it's effect factors related, so as to find a new potent agent for neurodegeneration diseases.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 Cin from excitotoxicity induced by quinolinic acid(QA). Fortheremore, the content of MDA, the activity of NOS, the concentration of free Ca2+, the content of the EAAs and IAAs were assaied and the apoptosis were observed so as to study the protection factors related to Cin.Results and conclusions:(1)Cin(1.2×10-6 mol/L,1.2×10-7 mol/L)could increase 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 Cin(1.2×10-6 mol/L,1.2×10-7 mol/L)could protect remarkably the primary hippocampus cells from the damage of excitotoxicity.(2)The content of MDA, the activity of NOS,the concentration of free Ca2+ and their rate of apoptosis of primary hippocampus neurons cocultured with QA were increased, Cin(1.2×10-6 mol/L,1.2×10-7 mol/L)could decrease the content of MDA, the activity of NOS and the concentration of free Ca2+, these differences were significant compared to those of models,and could relieve the apoptosis, so we presumed that the protection of Cin(1.2×10-6 mol/L,1.2×10-7 mol/L)from excitotoxicity maybe related with these factors.(3)The content of EAAs(Glutamic acid,Aspartic acid) and IAAs(γ-aminobutyric acid,Glycine,Taurine) and their rate of apoptosis of primary hippocampus neurons cocultured with QA were increased, Cin(1.2×10-6 mol/L,1.2×10-7 mol/L)could decrease the content of the AAAs, these differences were significant compared to those of models. The percent of increase of the EAAs' content between normal and model is lager than the percent of increase of the IAAs'. These effects were significantly different from each other. So we presumed that the excitotoxicity due...
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