| Background and objectiveAs our country gets into aging society, cerebrovascular disease becomes a major causing death and mutilation disease. Cerebrovascular disease, cardiac disease and malignant tumor are to constitute the three major causing death etiopathogenisis of human, especially the cerebral vascular dementia, Alzheimer disease, Binswanger and so on. These cerebral vascular diseases are induced by chronic cerebral ischemia. Their symptoms are hidden, progress gradually. Accordingly, to study on chronic cerebral ischemia and find out the effective cure and protect ways is very significant.Chronic cerebral ischemia is induced by the choronic insufficient brain blood supply, it makes the brain dysbolism and function decline. Chronic cerebral ischemia has the symptoms like dizzy, tinnitus, intelligence decrease, memory lower and impaired concentration, disorientation. Based on the reasonable grouping, Scholars made quantitative analysis to the rat's hippocampus CA1 and DG molecular layer. They found that, memory impaired rats have the obviously lower synaptophysin immunohisto-chemistry stain gray scale in hippocampus, and they have the negative correlation between average escape incubation and synaptophysin immunohisto chemistry stain gray scale in hippocampus and Dentate Gyrus (DG ) . These results are strongly hint: the aged hypomnesia is close correlated with the synaptophysin's change in hippocampus.Scholars had found that in their experiment, the express of N-Methyl-D-Asparate(NMDA)receptor-2B (NR2B ) mRNA in Vascular Dementia (VD) mouse's hippocampus CAl neuron grow downwards, accord with their study and memory results cut down. So they infer that may be the decrease express of NMDA receptor-2B mRNA in VD mouse's hippocampus CAl participates the VD invasive molecular biology mechanism. The mechanism of the decrease express of NMDA receptor-2B mRNA in VD mouse's hippocampus CAl, may be concerned with the hippocampus ischemia, neuron death and construction damage caused by oxygen-poor, or may be concerned with the damaged neurotransmission induced by long time neuron hypometabolism.dl-butylphthalide chemname is despin-3-normal- dl-butylphthalide ,it has the same construction with the laevorotation butyl phthalide get out from celery seeds, it's artificial synthetically racemic. Clinical research finding indicated that, dl-butylphthalide has the improve effection to acute ischemia stroke patients who have central nerve function damage, dl-butylphthalide can promote the patients' functional recovery. It's possible that the dl-butylphthalide can decrease the content of arachidonic acid, increase the level if nitrogen monoxidum and prostaglandin L2 in brain blood vessel endothelium, restrain the release of aminoglutaminic acid, decrease the Ca2+ density in brain cells, restrain the free radicle and elevate the antioxidase activity. The drug action effect are based on the mechanism above. This article aims to observe the effect of dl-butylphthalide on NMDA receptor-2B and Synaptophysin in hippocampus of aged rats after chronic cerebral hypoperfusion.Materials and methods1 Selected 80 healthy Wistar rats and distributed to 4 groups randomly, regardless of male or female, 20 rats each group. Group A: control group (sham operation plus); group B: ischemia group; group C: ischemia and low dose treatment group; group D: ischemia and high dose treatment group. Chronic cerebral ischemic rat model was established by permanent occlusion and snip of bilateral common carotid arteries. The rats of group B and D began to receive daily oral dose of 60mg/kg and 120mg/kg NBP (dissolved into 2ml oil) from the 61st day after the operation, which will last a month. The rats of groups A and B received the same volume of oil, which will last the same time.2 Chronic cerebral ischemic rat model was established by permanent occlusion and snip of bilateral common carotid arteries. Rats undergoing permanent bilateral occlusion and snip of the common carotid arteries were distributed into ischemia group or ischemia treatment group. Rats with bilateral common carotid arteries only isolated but not ligated and snipped were into control group.3 The data was handled with SPSS11.0 statistic software. The diference of every two groups was compared with one-way analysis of variance and LSD method, significant level isα= 0.05.Results1 The conditions of animal.All the rats were depressed, reacted slowly, ate little, after operation. The next day, sham groups recovered significantly, however the operation groups recovered slowly until 3-5 days. A week later, they were normal.2 The results of pathological section with HE stainingOnly a few degenerated and dead neurons were found, while most neurons were normal in morphology in group A. The number of degenerated and dead neurons significantly increased in group B compared with group A. The number of degenerated and dead neurons was less in group C compared with group B. The number of degenerated and dead neurons was less in group D compared with group C.3 The results of immunohistochemical for synaptophysinThe grey number of synaptophysin in hippocampus CA1 in rats brain of group A, B, C and D were: 156.38±3.69;125.62±11.52;142.77±3.95;150.01±4.98 respectively, and in hippocampus CA3 were154.10±4.27;120.47±6.49;140.16±5.07;146.47±4.86 respectively, and in hippocampus DG were 140.00±4.59;111.55±5.33; 128.05±4.48;134.22±4.19.The grey number of synaptophysin immunopositive cells in each part were markly decreased in group B comparing with group A.The difference between group B and group A was significant (P<0.05).The grey number of synaptophysin immunopositive cells in each part was markly increased in group C and group D comparing with group B.The difference between group C, D and group B was significant (P<0.05).The grey number of synaptophysin immunopositive cells in each part was markly increased in D group comparing with C group. The difference between group D and group C was significant (P<0.05).4 The results of immunohistochemical for NMDA receptor-2BThe grey number of NMDA receptor-2B in hippocampus CA1 in rats brain of groupA,B,CandDwere:169.54±3.36;135.00±6.48;155.97±3.97; 161.07±5.29respe ctively, and in hippocampus CA3 were 163.07±3.57; 130.28±7.81; 150.55±4.67; 155.00±5.15respectively, and in hippocampus DG were 151.62±4.34; 121.50±4.85;137.93±4.17;144.08±3.71.The grey number of NMDA receptor-2B immunopositive cells in each part were markly decreased in group B comparing with group A.The difference between group B and group A was significant (P<0.05).The grey number of NMDA receptor-2B immunopositive cells in each part was markly increased in group C and group D comparing with group B.The difference between group C, D and group B was significant (P<0.05).The grey number of NMDA receptor-2B immunopositive cells in each part was markly increased in D group comparing with C group. The difference between group D and group C was significant (P<0.05).Conclusion1 .Three months after chronic cerebral hypoperfusion, the expression of NR2B and synaptophysin in the CA1, CA3 and DG of hippocampus are markly decreased.2. dl-butylphthalide can increase the expression of NR2B and synaptophysin in rats'hippocampus after chronic cerebral hypoperfusion. |
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