| Objective: To observe the therapeutical effect of JiannaoYizhi decoction in vascular dementia model rats induced by chronic ischemia and investigate its partial mechanism. Methods: This study choose healthy male Wistar rats of 3-5 months, the rats were randomly divided into sham-operated group, model group, Donepezil group and JiannaoYizhi decoction high, medium and low dose group.The chronic cerebral hypoperfusion models were established by modified permanent bilateral occlusion of both commen carotid arteries(2VO).The regulated dose medicine was given to the survival models by intragastric administration,sham-operated group was given equivalent of physiological saline. Administered in each group after three weeks, Morris water maze experiment was adopted to evaluate the learning and memory ability of rats in each group, to compare the results of the group differences. Administered over 30 days, to decapitate, take out brain, and separate the right cerebral cortex immediately for measuring activity of SOD,content of MDA.The remaining brain tissue was fixed, the hippocampus and the left frontal lobe cortex were separated, and the sections were subjected to immunohistochemical methods.The changes of choline acetyltransferase (ChAT) expression of neurons of hippocampus and frontal lobe cortex were observed.Results:1. The Morris water maze test manifested: during place navigation test, escape latency of the model group was significantly longer than that of the sham-operated group(P<0.01), escape latency of JiannaoYizhi decoction high, medium dose group and the Donepezil group was shorter than that of the model group(P<0.01), moreover, there was no significant difference among the three groups; in probe test, number of times that the model group passed through original platform location decreased significantly compared with the sham-operated group (P<0.01), number of times that JiannaoYizhi decoction high, medium dose groups and Donepezil group passed through original platform location are more than the model group′s(P<0.01, P<0.05, P<0.05), and there was no obvious difference among the three groups.2. Compared with the sham-operated group,the model group had more obviously radical changes, the content of MDA increased (P<0.01), the activity of SOD lowered(P<0.01); compared with the the model group, the content of MDA of each treatment group was lower (P<0.01 or P<0.05), only the activity of SOD of JiannaoYizhi decoction high and medium dose groups increased significantly among the treatment groups(P<0.01, P<0.05); the content of MDA of JiannaoYizhi decoction high and medium dose groups were more obviously lower than that of the Donepezil group(P<0.01, P<0.05), the activity of SOD of JiannaoYizhi decoction high dose group increased more significantly than that of the Donepezil group(P<0.05).3. The result of expression of ChAT immunohistochemistry revealed: Neurons of hippo- campus, prefrontal cortex of model group with a loose, small size,ChAT staining positive light, compared with sham-operated group,the area of ChAT expression decreased significantly(P<0.01).Neurons of high,medium-dose groups and the donepezil group with more rules,more pronounced cytoplasmic ChAT-positive stain,ChAT expression area increased significantly than those in model group(P<0.01);the area of ChAT-positive expression of JiannaoYizhi decoction high dose group increased significantly than that of medium low dose group(P<0.05),and there was no significant difference compared with donepezil group(P>0.05).Conclusion:1. Chronic ischemia-induced VaD rat models which established by modified 2VO method basic simulated learning and memory decline and radical changes,the pathogenesis that the central cholinergic system was damage in patients with VaD, indicating that the model is successful.2. JiannaoYizhi decoction have stronger effect of anti-free radicals than Donepezil.3. JiannaoYizhi decoction and donepezil can decrease the injury of the central cholinergic system of VaD rat models that caused by chronic ischemia, so can improve cognitive dysfunction as a result of cerebral ischemia-induced.
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