| Abstract:Objective:To investigate regulatory effect and mechan-ism of Luzhou lychee seed extracts on cognitive disorder of rats with T2DM.Methods:The normal learning and memory male Sprague-Dawley(SD) rats were selected with Morris water maze,which were randomly divided into control group,model group,0.42mg·kg-1 donepezil group,0.69g·kg-1,1.39g·kg-1 and 2.78g·kg-1 lychee seed extract treatment group.The model of cognitive disorder in rats with T2DM were induced by high-fat and high-prorein diet for 3 months and peritoneal injection 27mg·kg-1 strep-tozotocin(STZ).Intragastric administration,one time every day for one month. Morris water maze examination was used to detect learning and memory ability of the T2DM rats,and blood glucose was measured by blood glucose meter,by means of radioimmunoassay to detect serum insulin and P-Amyloid Protein (Aβ) and Aβin hippocampus,and by means of enzyme linked immunosorbent assay(ELISA) to measure AGEs in hippocampus.AChE activity in Plasma and hippocampus were determined by chemical-colorimetric method.Brain of rats were poured into 4% paraformaldehyde for fix,and the brain was made by paraffin embedding,coronal microtome section. Hematoxylin-eosin and the immunohistochemical staining(SABC) were employed to observe the degree of injuried neuron and the positive expression of NF-κB on CA1 in hippocampus,and its integrated absorbance was analysised by Image pro plus 5.1 software of expression of NF-κB.Results:(1)Compared with the normal breeding group,the blood glucose was increased significantly (P<0.01), spatial learning and memory in rats were decreased significantly (P<0.01).(2)Compared with the control 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,0.69g·kg-1,1.39g·kg-1and 2.78g·kg-1 lychee seed extract can shorten the escape latency of rats (P<0.05,P<0.01),and prolong the time spent in target quadrant (P<0.05).2.78g·kg-1 lychee seed extract can increase the numbers of rats crossing platform and the run percentage of target quadrant(P<0.05).Compared with the treatment group,there are significant differences in the escape latency of rats,in the fifth day of the place navigation exercise (P<0.05,P<0.01).(3)Compared with the contral group,the plasma AChE activity,the serum insulin content,the Aβlevels in serum and hippocampal and AGEs content in hippocampus,all were increased significantly(P<0.01),and the activity of AChE in hippocampal tissue was decreaed(P<0.01).Compared with the model group,0.69g·kg-1,1.39g·kg-1 and 2.78g·kg-1 lychee seed extract all can decrease the plasma AChE activitythe serum insulin content, the Aβcontent in serum and hippocampus and AGEs in the hippocampus(P<0.01),but the activity of AChE of hippocampus was increased in treatment group.The three dose groups compared with each other,there are significant difference in the treatment group(P<0.01,0.05).(4)Under the light microscope(×400): the row of neurons is tight and order,nucleus is big and round,coloring of nucleus and endochylema are obvious and the nucleolus is clearness in the contral group.The row of neurons is rarefaction,the endochylema is thickening,and the nucleus is karyopyknosis and anachromasis in the model group.Above-mentioned neuron degeneration and injured were improved obviously in the treatment group.There was very few brownness grana in the nucleus of rats in the contral group,and sedimentation of brownness grana in the nucleus was increased obviously in the model group.Lychee seed extract can decrease sedimentation of brownness grana in the nucleus,and the effect is more obvious following drug dosage increased.The integrated absorbance of expression of NF-κB in hippocampus was decreased in the model group (P<0.01),and there is decreased obviously in treatment with lychee seed extract group(P<0.01), and there is significant differences among three dose groups (P<0.01, <0.05).conclusion:(1)The model of cognitive disorder in rats with T2DM were induced successfully by high-fat and high-prorein diet for 3 months and peritoneal injection 27mg·kg-1 streptozotocin(STZ).(2)Lychee seed extracts can improve cognitive disorder of rats with T2DM,and there is a dose-dependent.(3) The possible mechanism include:①By improving insulin resistance and decreasing blood glucose to reduce the Aβand Tau protein saccharified,and to reduce formation of SP and NFT.By decreasing the formation and accumulation of AGEs induced by hyperglycemia todecrease AGEs action on RAGE caused the cascade reaction of inflammatory reaction,oxidative stress and apoptosis damaged on hippocampal neurons.②By decreasing accumulation of Aβin hippocampus to reduce direct neurotoxic effect of Aβand interaction between Aβand NF-κB.③The cause has to do with improving function of central cholinergic neurone in cognitive disorder of rats with T2DM and increasing synthesis of ACh to raise relative amount and keep dynamic equilibrium of ACh in brain. |
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