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Protection Effect And Mechanism Of Trans-Resveratrol For β- Amyloid Peptide-Induced Dementia

Posted on:2016-12-12Degree:MasterType:Thesis
Country:ChinaCandidate:J J WuFull Text:PDF
GTID:2284330479475369Subject:Neurology
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Objective: To observe trans-resveratrol(TR)-induced protective effects and mechanism on demented rats that are caused by amyloid β-protein fragment 25-35(Aβ25-35).Methods: We Divided standard rats into 3-month and 20-month two groups, and separated these two groups into 4 subgroups randomly: sham group, model group, TR low and high-dosages group. After using Aβ25-35 to make dementia models, then infusing stomach by TR to that models. Ten,forty mg?kg-1?d-1 TR was administrated to Low- and High-dosages groups respectively, and 0.9%Na Cl(1 ml/100 g)was administrated to sham group and model group for consecutive 10 days. We Used Morris water maze to test the learning and memory abilities. Caspase-3 and DNA polymerase-γ expression in hippocampus were detected by RT-PCR(real-time and quantitative PCR). Caspase-3, APP and DNA pol-γ expression in hippocampus were detected by WB. Transmission electron microscope was used to observe number of synaptic and changes of mitochondria in the hippocampus.Results: Navigation test showed that escape latency in sham group was(50.9±27.4 in the first day, 49.8±24.9 in the second day, 34.8±15.4 in the third day, 23.8±12.3 in the fourth day); model group was(88.4±19.8 in the first day, 68.3±29.3 in the second day, 51.1±23.2 in the third day, 43.9±20.2 in the fourth day), TR low-dosages group was(78.4±17.0 in the first day, 61.3±24.6 in the second day, 48.1±18.7 in the third day, 37.9±15.8 in the fourth day); TR low group was(78.4±17.0 in the first day, 61.3±24.6 in the second day, 48.1±18.7 in the third day, 37.9±15.8 in the fourth day); TR high-dosages group was(67.7±20.7 in the first day, 54.0±26.2 in the second day, 40.4±23.1 in the third day, 33.2±20.4 in the fourth day); compared with the sham group, model group and TR low, high-dosages group prolonged(P<0.05). Space exploration experiments revealed that across platform times in sham group was 6.3±3.5, model group was 2.1±1.8, TR low group was 2.7±1.7, TRhigh-dosages group was 4.4±2.4, compared with the sham group, model group and TR low, high-dosages groups were fewer than the sham group(P<0.05). RT-PCR was used to detect the expression of caspase-3 and DNA pol-γ, model group was higher than sham group( P<0.01), TR had a obvious down-regulation effect(P<0.01) on caspase-3 and DNA pol-γ. The expression quantity of 3-month rats was higher than 20-months rats in model group(P<0.05). The expression quantity of 3-month rats is higher than 20-months rats in drug group(P<0.05). WB was used to detect the expression of caspase-3, DNA pol-γ and APP, the expression quantity of mdel group was higher than the sham group(P<0.05), TR had a obvious down-regulation effect on caspase-3, DNA pol-γ and APP(P<0.05). Transmission electron microscope was applied to observe the number of synaptic in hippocampal,compared with sham group, model group was fewer than sham group(P<0.05), compared with model group,TR low and high-dosages groups were more than model group(P<0.05). The swollen and disrupted mitochondria were frequently found in the hippocampal area of model group. A few disrupted mitochondria were still found in the hippocampal areas of TR low and high-dosages groups, but it obviously improved that crest gradually restored.Conclusion: It may be related to downgrade the expression of caspase-3, DNA polymerase-γ and APP that TR has protective effects on para-hippocampal cortical neuron.
Keywords/Search Tags:Trans-resveratrol, demented rats, Caspase-3, DNA polymerase-γ
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