| Objective:To investigate the intervention effect and mechanism of Luzhou lychee seed saponins on rats with Alzheimer's disease(AD). Methods:The normal learning and memory male Sprague-Dawley(SD) rats were selected with Morris water maze,which were randomly divided into sham operation group, model group,0.42mg·kg-1 donepezil group,0.17g·kg-1,0.34g·kg-1 and 0.68g·kg-1 lychee seed saponins treatment group. The model of rats with AD were induced by intracerebroventricular injection of 3mg·kg-1 streptozotocin(STZ). Intragastric administration,one time every day for one month. Morris water maze examination was used to detect learning and memory ability of the AD rats, and AChE activity in Plasma and hippocampus were determined by chemical colorimetric method.β-Amyloid Protein (Aβ) in serum and hippocampus were determined by means of radio-immunoassay,and by means of enzyme linked immunosorbent assay(ELISA) to measure AGEs in hippocampus. Brain of rats were poured into 4% paraformaldehyde for fix,and the brain was made by paraffin embedding,coronal microtome section. TdT-mediated dUTP nick end labeling(TUNEL) and the immunohistochemical staining (SP) were employed to observe the degree of neuronal apoptosis and the positive expression of Cyt-c in hippocampus,the positive rate of apoptotic cells was calculated by GD-10.0 image analysis system and the average optical density was analysised by Image pro plus 5.1 software of expression of Cyt-c. Results:(1)Compared with the sham operation group, learning and memory in rats of the other operation groups were decreased significantly (P<0.01). (2)Compared with the sham operation group, the escape latency of rats in model group was significantly increased (P<0.01),the numbers of rats crossing platform,the time spent in target quadrant and the run percentage of target quadrant was decreased significantly (P<0.01). Compared with the model group,0.17g·kg-1,0.34g·kg-1 and 0.68g·kg-1 lychee seed sapopnins can shorten the escape latency of rats (P<0.05, P<0.01),0.68g·kg-1 lychee seed sapopnins can increase the numbers of rats crossing platform,the time spent in target quadrant and the run percentage of target quadrant (P<0.05).0.34g·kg-1 lychee seed sapopnins can increase the numbers of rats crossing platform(P<0.01). Compared with the treatment groups,there are significant differences in the escape latency of rats, in the fourth and fifth day of the place navigation exercise (P<0.05). (3)Compared with the sham operation group, the AChE activity in serum and cerebral cortex, the Aβlevels in serum and hippocampal and AGEs content in cerebral cortex,all were increased significantly(P<0.01), Compared with the model group,0.17g·kg-1,0.34g·kg-1 and 0.68g·kg-1 lychee seed sapopnins can decrease the AChE activity in serum and cerebral cortex, the Aβlevels in serum and hippocampal and AGEs content in cerebral cortex (P<0.01). The three dose groups compared with each other, the Aβlevels in hippocampal and AGEs content in cerebral cortex was significantly different between the low dose and high dose group(P<0.05). (4)Under the light microscope (×400):a few cell nucleus were stained in brown in hippocampal CA1 area in the sham operation group and a number of cell nucleus with brown, uneven, showed a ring-like structure were seen in hippocampal CA1 area in the model group,which the positive rate of apoptotic cells increased obviously.In 0.17g·kg-1,0.34g·kg-1 and 0.68g·kg-1 lychee seed sapopnins,the number of cell nuclei with brown decreased significantly,so the same as the positive rate of apoptotic cells(P<0.05),but there were no differences among the various dose groups. The pyramidal cell nucleus were stained blue and the cytoplasm of brown granules were not been found in hippocampal CA1 area in the sham operation group. Spotty distribution of positive brown granules can be seen in hippocampal CA1 pyramidal cells plasma in the model group, the average optical density (AOD) of Cyt-c immunoreactive cells were significantly enhanced (P<0.01).In the treatment group with 0.17g·kg-1,0.34g·kg-1 and 0.68g·kg-1 lychee seed sapopnins, the spotty distribution of brown particles reduced Significantly, the average optical density (AOD) of Cyt-c immunoreactive cells are lower (P<0.01,0.05), but there were no differences among the various dose groups. Conclusion:1.The model of rats with AD were induced successfully by intracerebroventricular injection of 3mg·kg-1 streptozotocin(STZ) 2.Lychee seed sapopnins can improve learning and memory of rats with AD,and there is a dose-dependent.3.The possible mechanism include:(1)Inhibit AChE activity in the central. (2)By improving insulin resistance, antioxidant and anti-inflammatory effects①reduce the formation of AGEs②promote Aβdecomposition and reduce Aβsecretion, thus reduce the deposition of Aβin the hippocampus③inhibit the releasement of Cyt-c,reduce the apoptosis of hippocampal neurons.
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