The Experimental Study Of The Effect Of Probucol Against Vascular Dementia Rats On Activity Of SOD, Content Of MDA In Hippocampus Tissue

Objective: Vascular dementia (VD) is a common disease in clinic, whichis always accompanied with cerebral vascular disease, and it is caused by aseries of cerebral vessels factors. Vascular Dementia is a kind of dementiasyndrome with recognition functional disturbance. It not only takes long-termanguish to the patient，but also poses heavy burden on the family and society.For nearly a century, the increasement of human average age led to theincreased dementia, especially vascular dementia, which was considered as thesecond larggest cause of dementia after Alzheimer’s disease in Europe may bemore important in Asia. Therefore studies on vascular dementia is especiallyimportant. For the past few years, the relationship between free radical injuryand vascular dementia was a hot issue being paid attention to. Malondialde-hyde (Maleic Dialdehyde, MDA) in tissue is the main metabolite of lipidperoxide and Superoxide Dismutase (Superoxide Dismutase, SOD) activityindirectly reflects the body’s ability to remove oxygen free radicals. Thepurpose of this study was to understand the vascular dementia rats with thechange of SOD and MDA in the hippocampus, to further explore therelationship of VD and oxidative damage, and further discuss intelligence toimprove the situation of VD model rats and SOD and MDA of hippocampus,for clinic use provide experiment basis on treatment of VD.Methods: Sprague-Dawley (SD) rats were randomly divided into blankmodel group, sham-operated group and probucol group. Each group has12rats. Permanent occlusion of the bilateral common carotid arteries induced astate of chronic and moderate ischemia associated with VD in rats. Thecriteria of animal model were as follows: Morris water maze test was performed1day of training in all groups of rats7days after operation.According to the reference value of the full-time average escaping latentperiod of the rats in the sham-operated group, we calculated theproportion-one minus the reference value divided by the full-time averageescaping latent period of the operated groups. If the proportion>20%, the ratis regarded as VD rats. Probucol group rats were administered with500mg/kg/d probucol by intragastric administration with the same volume ofsodium salt of carboxy-methyl cellulose.8-week later,5-day Morris watermaze test was established to observe the alteration in behavior of rats,including the mean escape latent period within the first4days, the traversingtimes through the flats within120seconds at the5th day. The hippocampuswere taken immediately and made to10%homogenate. The levels of SOD andMDA were measured by zanthine oxidase method and Thibabituric Acid(TBA) method respectively. The effect of probucol on the improvement ofVD rats intelligence was evaluated by detecting the SOD activity, MDA leveland neuron morphological structure in hippocampus tissue.Results:1The general situation of observationAfter operation, rats could not eat, exercise decrease, reaction was slow,but no limb paralysis was found. The body weight decreased gradually withinthe first6days, reduced about5g every day, the weight of rats began torecover at the seventh days. The results are consistent with the literature.2Determination of behaviorThe learning and memory of VD rats were observed by Morris watermaze, the escape latency of rats represents the learning ability, the escapelatency is short and the learning ability is strong. Escape latent periods weresignificantly longer in the blank model group compared with thesham-operated group and probucol group (P<0.01), escape latent periods weresignificantly shorter in the probucol group compared with the blank modelgroup (P<0.01). At the5th day, traversing times significantly decreased in theblank model group compared with the sham-operated group (P<0.01), traversing times significantly increased in the probucol group than that in theblank model group (P<0.01). with the training time and the increase of thenumber of training, the rats looked for the platform in the way of changingtime, looked for the platform in the time shortened, indicating that learningexercise could enhance memory ability.3Determination of brain tissue SOD activity and MDA contentSOD activity decreased significantly with a significant in the blankmodel group compared with the sham-operated group (P<0.01); The contentof MDA in the hippocampus significantly increase in the blank model groupthan the sham-operated group (P<0.01). SOD activity increased significantlyin the probucol group compared with the blank model group (P<0.01), but thecontent of MDA significantly decreased (P<0.01).4Hippocampal nerve cell morphological observationThe structure of nerve cells in the hippocampus CA1region layer in thesham-operated group was compacted, nervous nuclei was integral, and thecytoplasm was rich. In the blank model group, the cells of the hippocampusCA1region are disordered, the number of nerve cells obviously reduced,many cells became incomplete, some formed pieces, matrix was loose andmicro empty bubble formed. In probucol treatment group, the cells shape ofhippocampus CA1region closed to normal, the hippocampus cells arrangedclosely, the level of rich, cell number was significantly more than the blankmodel group, nerve cells were intact, cytoplasm was abundant and a smallamount of cell degeneration was found.Conclusions:1Permanent occlusion of bilateral common carotid arteries of rats canreproduced VD model.2MDA content increased significantly and SOD activity decreasedsignificantly in VD rats, indicating the participation of oxidative damage inthe VD process.3Probucol can improve the level of knowledge and pathological changes,improve learning and memory abilities. 4Probucol can improve SOD activity and reduce the content of MDA inthe hippocampus of VD rats, suggesting that anti-lipid per oxidation may beone of the mechanisms that probucol improves spatial learning and memoryimpairment in VD rats.