| Vascular dementia（VD），the second most common cause of dementia after Alzheimer’sdisease and the most common cause of dementia in the elderly, is defined as loss of memoryand cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesionsdue to cerebrovascular disease.People so far is not clear to the pathogenesis of VD,so theonly treatment is based on the symptoms and we can’t stop or reverse the process of dis-ease.In recent years,scholars paid a lot of attention on studying the reason and the pathoge-nesis of VD for prevention and better treatment,and they found that mitochondrial play animportant role. In this study we establish repeatability，effectiveness vascular dementia（VD）models by permanent occlude common carotid arteries of rats t with1week interval betweenartery occlusions,and study the mitochondrial bioenergetic deficit by assess the cytochrome coxidase（COX） activity, the expression of cytochrome c oxidase （COX） subunitⅣand pyru-vate dehydrogenase （PDH） subunit A1,the production of hydrogen peroxide（H2O2） of state4respiration and the oxygen consumption of state3respiration.of mitochondria isolated fromhippocampal of rats.Methods: After the training of Morris water maze place navigation experiment,132healthy Wistar rats were randomly assigned to:2month ischemia group （n=30）,3monthischemia group （n=30）,4month ischemia group （n=30）,2month pseudooperation group（n=14）,3month pseudooperation group （n=14）,4month pseudooperation group （n=14）. Es-tablish vascular dementi（aVD）models by permanent occlude common carotid arteries of ratst with1week interval between artery occlusions. Observed the postoperative state. Measuredthe ability of learning and memory with Morris water maze test. Isolated mitochondria fromhippocampal of rats of ischemia group and pseudooperation group.Using spectrophotometerto assess the activity of COX and the expression of PDHA1and COX IV was assessed byWestern blot analysis. The Amplex Red hydrogen peroxide assay was used to determine therates of hydrogen peroxide production of mitochondria in state4respiration. Oxygen con-sumption of state3respiration was assessed by using A65N-1oxygen probe.Results:1. The escape latency in2month ischemia group was significantly longer than that in2 month pseudooperation group （P <0.05）. The escape latency in3month ischemia group wassignificantly longer than that in3month pseudooperation group （P <0.05）. The escape la-tency in4month ischemia group was significantly longer than that in4month pseudoopera-tion group （P <0.05）.2. The COX activity was significantly decreased in ischemia group as compared topseudooperation group（P <0.05）. While the COX activity in4month ischemia group wassignificantly decreased as compared to2month ischemia group （P <0.05） and3monthischemia group （P <0.05）.3. COX IV expression was significantly decreased in ischemia group as compared topseudooperation group （P <0.05）.As the time went by the expression of COX IV in ischemiagroup decreased more and more.4. PDHA1expression in3month ischemia group was significantly decreased as com-pared to3month pseudooperation group （P<0.05）. PDHA1expression in4month ischemiagroup was significantly decreased as compared to4month pseudooperation group （P<0.05）.As the time went by the expression of PDHA1in ischemia group decreased more and more.5. There were significant increases in the rate of state4respiration hydrogen peroxideproduction of mitochondria isolated from hippocampus of rats in3month ischemia groupand4month ischemia group as compared to month-matched pseudooperation group（P<0.05）.While the rate of state4hydrogen peroxide production in3month ischemia groupwas significantly increased as compared to2month ischemia group （P<0.05），and the rate ofstate4hydrogen peroxide production in4month ischemia group was significantly increasedas compared to3month ischemia group （P<0.05）.6. Oxygen consumption of state3respiration of mitochondria isolated from hippocam-pus of rats in ischemia group was significantly less than that of month-matched pseudoope-ration group （P<0.05）. While the oxygen consumption of state3in3month ischemia groupwas significantly less than that of2month ischemia group （P<0.05），and the oxygen con-sumption of state3in4month ischemia group was significantly less than that of3monthischemia group （P<0.05）.Conclusion:1. Established vascular dementia rat model through permanent bilateral occlusion of thecommon carotid arteries in the rat with1week interval between artery occlusions success-fully. Evaluation of histologic changes by using Morris water maze test demonstrated that the model is reliable.2. There were decrease in activity of COX and the expression of COXⅣ in vasculardementia rat models,and as the time went by the decreases became more and more se-rious.They demonstrate further that the activity of COX and the expression of COXⅣ takepart in the mechanisms of vascular dementia.3. There was a decreases in the expression of PDHA1in vascular dementia rat mod-els,and as the time went by the decrease became more and more serious.It demonstrates fur-ther that the expression of PDHA1takes part in the mechanisms of vascular dementia.4. There was a increase in the the rate of state4respiration hydrogen peroxide produc-tion of mitochondria isolated from hippocampus of vascular dementia rat models, and as thetime went by, the increase became more and more serious.It demonstrates further that theincrease in the the rate of state4respiration hydrogen peroxide production of mitochondriatakes part in the mechanisms of vascular dementia.5. There was a decrease in the oxygen consumption of state3respiration of mitochon-dria isolated from hippocampus of vascular dementia rat models,and as the time went by,thedecrease became more and more serious.It demonstrates further that the disruption of mito-chondrial respiration takes part in the mechanisms of vascular dementia.6. There’s a mitochondrial bioenergetic deficit of hippocampus in vascular dementia ratmodels caused by chronic ischemic, and the mitochondrial bioenergetic deficit may take partin the mechanisms of vascular dementia... |
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