Effect Of Ruanmailing Koufuye On Learning And Memory In Rats With Vascular Dementia And Research Of The Mechanisms

Objective:To detecte superoxide dismutase(SOD),malonaldehude (MDA), glutathione(GSH) of the hippocampal tissue in rats with vascular dementia.To explore the change of morphous ,the expression of apurinic/apyrimidinic endonuclease/redox factor 1(APE/Ref-1),and the neuronal apoptosis of the hippocampal CA1 subregion in rats with vascular dementia.To study the effection of Ruanmailing koufuye on learning and memory and those indexes mentioned above,and approach the possible mechanisms of Ruanmailing koufuye on improving vascular dementia.Methods:The rats were divided into 5 groups at random,which were artifical operation group ,model group,nimodipine group,high dose of Ruanmailing koufuye group and low dose of Ruanmailing koufuye group ,the rats were lavaged with different drugs or saline.We established a VaD rat model after chronic cerebral hypoperfusion caused by permanent bilateral common carotid arteries occlusion(2VO). Morris water maze experiment was adopted to test learning and memory in rats of each group. Colorimetric method was used to detect the SOD activity, the MDA and GSH content of the hippocampal tissue in rats of each group, changes of morphous in the hippocampal CA1 subregion in rats of each group was observed by hematoxylin and eosin (HE) stain,expression of the APE/Ref-1 protein was measured by immunohistochemical analysis,apoptosis was observed by in site end-labeling of fragmented DNA using the tereminal deoxynucleotidyl transferase reaction(TUNEL).Results:1.Compare with artifical operation group ,the SOD activity of hippocampal tissue was reduced in model group ,and the GSH content was decreased ,but the MDA content was higher.The quantity of APE/Ref-1 positive cells was less in the hippocampal CA1 subregion of model group than that of artifical operation group,the quantity of apoptotic neurons in the hippocampal CA1 subregion of model group was more than that of artifical operation group. HE stain showed that some of the hippocampal CA1 subregion neurons were karyopyknotic or absent,and the cell layers of this region were incomplete.2.Be treated with Ruanmailing koufuye or nimodipine,the SOD activity of hippocampal tissue in rats with vascular dementia was raised ,and the GSH content was increased ,but the MDA content was decreased.The losing of the APE/Ref-1 positive cells in the hippocampal CA1 subregion was repressed in rats with vacular dementia treated with Ruanmailing koufuye or nimodipine,also, the quantity of the TUNEL positive cells was decreased,the morphous in the hippocampal CA1 subregion were improved in rats with vascular dementia treated with Ruanmailing koufuye or nimodipine.Among these groups, the therapeutical effect of high dose of Ruanmailing koufuye was better than low dose and nimodipini groups. Morris water maze experiment showed that ,be treated with high dose of Ruanmailing koufuye or nimodipine,the learning and memory were improved in rats with vascular dementia,and the therapeutical effect of high dose of Ruanmailing koufuye was better than the nimodipini group,while there was not obviously difference between low lose group and model group.Conclusions:1.After occlusion of bilateral common carotid arteries,the free radical metabolism of hippocampal tissue in rats was unbalanced, resulted in the accumulation of Oxygen free radical (OFR) ,the expression of APE/Ref-1 protein in hippocampal CA1 subregion was repressed at the same time ,so the quantity of the apoptotic neurons was increased , and some of the neurons would be absent.Maybe this was one of the mechanisms in change of learning and memory in rats with chronic cerebral ischemia .2.Be treated with Ruanmailing koufuye or nimodipine,the SOD activity of hippocampal tissue in rats with vascular dementia was raised ,and the GSH content was increased , result in the raisen of antioxygenic potential ,the losing of the APE/Ref-1 positive cells in the hippocampal CA1 subregion was repressed in rats with vacular dementia treated with Ruanmailing koufuye or nimodipine, so, the quantity of the TUNEL positive cells was decreased,maybe this was one of the mechanisms in the improving of learning and memory in rats with vascular dementia .Among these groups, the therapeutical effect of high dose of Ruanmailing koufuye was better than low dose and nimodipini groups.