THE RESEARCH ON MECHANISMS OF AMYLOID- β PROTEIN INDUCING ALZHEIMER'S DISEASE IN RAT AND EFFECTS OF NIMODIPINE TREATMENT

0bjective In order to clarify the mechanism of the neurotoxics of Aβ, we studied the effects on the rCBF, extra-cellular amino acid (EAA), apoptosis and Bcl-2 protein expression, and their relationship with learning and memory deficiency. Methods Aβ was injected into NBM in rats to establish the AD model, learning and memory abilities were observed by Y-maze. The rCBF was measured by hydrogen clearance method. The EAA was detected by microdialysis in vivo with HPLC. The apoptosis and Bc1-2 protein expression was examined by flow cytometry. The male SD rats were divided into three groups: the model group was injected Aβ (10 μ g) into NBM of the rat. The control group was injected NaC1 (0.9%) in the same way. The treatment group was made with intraperitoneal injections of Nimodipine for 2 weeks after A β injections. Results The administration of Aβ into rat′s NBM could lead to the loss of learning and memory abilities. It was found that in frontal cortex and hippocampus, the rCBF decrease, however, with no trend of progressive decline. On the other hand, the levels of EAA increased, especially glutamate. Furthermore, A β significantly induced neurons apoptosis of frontal cortex and hippocampi cell, and upregulated the expression of the bcl-2. The Nimodipine might entirely improve rCBF of AD rats nearly to normal level, lessen the release of EAA and augment restrain neurotransmission. It might reduce the apoptosis partly, but it couldn't improve the learning and memory disorders completely. Conclusion The results implied that the neurotoxic effect of Aβ exists multi-mechanism.