| Vascular dementia is commonly defined as a syndrome, include brain damagecaused by a series of cerebrovascular disease, with severe memory loss and cognitivedysfunction. Ischemic cerebrovascular disease is the primary etiology. Chroniccerebral ischemia, caused by various factors, is a common pathophysiological processin nervous system. While, it is considered to be the common pathophysiologicalprocesses of VD, AD, Binswanger disease and other diseases. Thus, chronic cerebralischemia has become the main research direction of pathogenesis of vasculardementia.In the vascular dementia model established through permanent bilateral carotidartery ligation, which simulates vascular dementia caused by chronic cerebralischemia, we can detect the blood supply decrease of the hippocampus, cerebralcortex and other areas, the cell loss induced by neuronal apoptotic, the level drop ofacetylcholine, the changes of energy metabolism and oxidative stress and so on.Ourprevious study found that chronic cerebral ischemia in early multiple synaptic proteinsassociated with mitochondrial metabolism has changed.Mitochondrial is the energyplants of cells, but also it produce the most part of ROS in cells. Naomaitai istraditional Chinese medicine preparation by red ginseng, Panax, angelica, Salvia andother components, which is benefit for blood circulation. Naomaitai decreasedoxidative stress caused by chronic cerebral ischemia,but the mechanism of improvingcognitive function is not defined.Objective:1. Establish vascular dementia rats model, and investigate its mitochondrial damagemechanisms. 2. Investigate the effects of Naomaitai on cognitive function, apoptosis ofhippocampus and cortical neuronal in vascular dementia rats model, and explore thepathology of Naomaitai improve vascular dementia cognitive function and themechanism of mitochondrial.Methods:1. Establish the vascular dementia rats model through permanent bilateral carotidartery ligation, and the postoperative rats were given different doses of Naomaitaiorally six weeks. Morris water maze test was used to detect the change of cognitivefunction.2. HE staining is used to detect the neurons morphological changes of hippocampalCA1and frontal cortex.3. Detecte the mitochondrial function of vascular dementia rats brain, includingmitochondrial reactive oxygen species (ROS), manganese superoxide dismutase(SOD), swelling of mitochondria, membrane potential, etc; detecte the expression ofbrain mitochondria Sirt3PGC-1α protein by western blot.Results:1. Place navigation tests show that, compared with sham-operated rats, the incubationperiod of model rats is significantly longer, and there is a significant differencebetween them (P<0.01). In the start four days, the incubation period of sham-operatedrats had a significantly decrease, and became stable on the fifth day. While in the startthree days, the incubation period of the model group rats decreased slowly, and on thefourth day it had a significantly decrease then into the plateau. Compared with themodel group, the incubation period of the Naomaitai rats were significantly reduced(P<0.05). In morris water maze test, we found that the original platform across timeand frequency of the model group were reduced significantly (P<0.05), described thatthe model rats group decreased memory capacity. The original platform across timeand frequency of the high-dose group had a significant improvement, and had asignificantly difference between the high-dose group and the model group (P<0.05).From the trajectory of morris water maze test, we found that the trajectory of the model group was edge-type, the trajectory of the sham group was goal-type moreconcentrated in the the third quadrant as the former platform, the trajectory of theNaomaitai group had significantly improvement, especially high-dose.2. From the results of HE staining biopsy, we found that, Compared with the shamgroup, the number of normal neurons in the hippocampal CA1region and prefrontalcortex reduced significantly, with severe apoptosis. In Naomaitai administration group,cell morphology, arrangement and others improved significantly.3. The generation of mitochondrial ROS of the chronic ischemic brain model group,compared with the sham group, increased significantly (P<0.05). Naomaitaiadministration, compared with the model, could reduce mitochondrial ROS (P <0.05).The mitochondrial swelling of chronic cerebral ischemia model is significant, whilethe Naomaitai administration weakened mitochondria swelling. The mitochondrialmembrane potential of Model group rats after chronic cerebral ischemia decreasedsignificantly, while Naomaitai administration improved it (compared with the modelgroup, low dose group P<0.05, the high-dose group P<0.01). The mitochondrial SODactivity of model group rats after chronic cerebral ischemia was significantlydecreased, while Naomaitai administration can increase mitochondrial SOD activity.Naomaitai can improve the function of mitochondria. The level of mitochondria Sirt3and PGC-1α protein in chronic cerebral ischemia group was lower significantly,compared with the sham group (P<0.05).Compared with the model group, theexpression level of two types of protein in Naomaitai treated rats was significantlyhigher (P<0.05).Conclusion:1.Chronic cerebral ischemia can induce cognitive dysfunction.2. Morris water maze detected that Naomaitai could improve cognitive function andspatial learning and memory abilities in vascular dementia rats.3.Chronic cerebral ischemia caused by mitochondrial dysfunction, ROS increasedproduction, decreased SOD activity levels, Sirt3and PGC-1α protein expression wasinhibited, leading to cognitive impairment. 4.Naomaitai may improve mitochondrial function, improving Sirt3and PGC-1αprotein expression, suggesting that its regulation of oxidative stress to improvecognition. |
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