| OBJECTIVE1. To study the effects of Aβ25-35 on the learning and memory abilities and on the protein expression of hyperphosphorilated tau(Pser404-tau), acetyltransferase(ChAT) and activities of acetylcholinesterase choline(AchE) in cortex and hippocampus after Aβ25-35 were injected into the right amygdala of rats.2. To explore the effects of cerebral ischemia on AD by performing a cerebral ischemia operation on AD rats.3. To discuss whether cerebral ischemia would lead to the pathological changes of AD by observing the changes of Pser404-tau, ChAT and AchE in CI rats.4. To investigate the treatment mechanism of Puerarin by observing the effects of Puerarin on AD rats and CI rats.METHODS1. Models: the AD models: The AD models were established by injecting Aβ25-35 (5.0nmol/3μl) slowly into the right amygdala under the stereotexic instrument when animals were anesthetized with 0.4% sodium pentobarbital. The CI models: The SD rats were anesthetized, parted from bilateral common carotid arteries, occluded the left common carotid arteries permanently, shut off the right common carotid arteries for 60 minutes transiently. The AD+CI models: The AD models underwent a cerebral ischemic operation at 14th day postinjection.2. Puerarin was administered (80mg/kg/d, intraperitoneally) at 14th day postinjection/on the first day postoperation. Puerarin was administered for 7days.3. The learning and memory abilities were measured by Y-maze before experiment and at 14th day, 21st day postinjection.4. All animals sacrificed after 21st day postinjection/7th day postoperation. The positive cell number of Pser404-tau, ChAT in cortex and hippocampus was measured with immunohistochemistry. The contents and activities of AchE in hippocampus were detected by spectrophotometer.RESULTS1. The effects of Aβ25-35 and CI on SD rats: The learning and memory ability of AD models had been impaired;Compared with the sham-operation group, in the AD models, the positive cell number of Pser404-tau in cortex and hippocampus was increased significantly and the positive cell number of ChAT was decreased markedly(P<0.01), the content and activities of AchE in the right hippocampus declined signigicantly(P<0.05), but the content and activities of AchE of the left hippocampus were not alterative(P>0.05). The positive cell number of Pser404-tau was increased and the positive cell number of ChAT was decreased(P<0.05), In the CI models, the content and activities of AchE in bilateral hippocampus were descend(P<0.05).2. The effects of cerebral ischemia on AD: Compared with AD models, The learning and memory ability of AD+CI models had been weaken severely; the positive cell number of Pser404-tau, ChAT was increased and decreased respectively(P<0.05); the content and activities of AchE were descended in the right hippocampus(P<0.05).3. The learning and memory impairment of AD models were improved by Puerarin remarkably(P<0.05); Compared to the AD group, the expression of Pser404-tau was decreased remarkably(P<0.05), the expression of ChAT and activities of AchE were increased significantly in Puerarin group(P<0.05).CONCLUSION1. The toxic role of Aβ25-35 injected into the unilateral amygdala of rats can induce tau protein hyperphosphorylation and dysfunction of the cholinergic system.2. The cerebral ischemia can lead to the changes of AD.3. The cerebral ischemia might aggravate the impairment of Alzheimer disease.4. Puerarin might reduce pathology reaction of AD, improve the learning and memory function of AD models. The treatment mechanism of Puerarin might be related to restraining the neurotoxicity ofβ-amyloid peptide(Aβ), expanding cerebral blood vessel, improving the microcirculation, restraining Pser404-tau protein hyperphosphorylation and increasing nerve center cholinergic function.
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