Resvertrol improves memory in AD rats by down-regulating expression of -APP in hippocampus
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摘要: 目的探讨白藜芦醇(resvertrol, Res)对阿尔茨海默病(Alzheimer's disease, AD)大鼠学习记忆及β-淀粉样前体蛋白(β-APP)表达的影响。方法采用去卵巢合并D-半乳糖(100 mg/kg)注射制备AD大鼠模型, 60只雌性Wistar大鼠随机分为模型组、白藜芦醇低、中、高剂量组(20、40、80 mg/kg)、戊酸雌二醇组(0.8 mg/kg)及假手术组(蒸馏水), 连续灌胃12周, 利用Morris水迷宫检测大鼠空间记忆能力;Western blot检测大鼠海马中β-APP表达。结果随着训练天数增加, 各组大鼠逃避潜伏期逐渐缩短, 与模型组比较, 白藜芦醇80 mg/kg组、戊酸雌二醇组大鼠逃避潜伏期[分别为(16.49±4.18)、(17.05±2.71)s] 明显缩短, 穿越平台次数[分别为(3.90±0.97)、(3.44±0.63)次]明显增加 (P<0.05), 白藜芦醇各组大鼠在目标象限内停留时间延长(P<0.05);白藜芦醇20、40、80 mg/kg组大鼠海马β-APP蛋白表达水平[分别为(0.57±0.054)、(2.63±0.50)、(0.28±0.043)]较模型组(0.27±0.057)明显下降(P<0.05)。结论白藜芦醇可以改善AD大鼠的空间记忆能力, 其机制可能与抑制海马β-APP的表达有关。
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关键词:
- 白藜芦醇 /
- 阿尔茨海默病(AD) /
- Morris水迷宫 /
- -淀粉样前体蛋白(-APP)
Abstract: ObjectiveTo evaluate whether long-term resvertrol(Res)treatment could result in the attenuation of spatial memory impairment in Alzheimer's disease(AD)rats and its mechanism.MethodsSixty female Wistar rats were divided into an AD model group(treated with ovariectomy[OVX]plus D-galactose[Gal] at 100 mg/kg),low,moderate,and high Res groups(OVX,Gal and Res at 20,40,80 mg/kg),estradiol valerate group(OVX,Gal and estradiol valerate at 0.8 mg/kg),and sham control group.At the end of 12 weeks,spatial memory was checked with Morris water maze test(MWM) and the expression of β amyloid precursor protein(β-APP)in hippocampus of the rats was test with Western blot.ResultsThe escape latency to find the submerged platform significantly declined in the rats of all groups.Moreover, the latency in the rats of 80 mg/kg Res(16.49±4.18 s)and estradiol valerate treatment group(17.05±2.71 s)decreased significantly,while the times of crossing over the platform site for the rats in 80 mg/kg Res(3.90±0.97)and estradiol valerate treatment group (3.44±0.63)increased markedly compared with that of the model group(1.22±0.45)(P<0.05).The time of stay in the target quadrant for the rats in all of the Res treatment groups was longer than that of the model group(P<0.05).The expression of β-APP in hippocampus in the rats of 20,40 and 80 mg/kg Res treatment groups were 0.57±0.054,2.63±0.50,and 0.28±0.043,respectively,with significant decrease compared with that of the model group(0.27±0.057)(P<0.05).ConclusionThe results suggest that Res is helpful in protecting AD rats from developing memory decline by decreasing the expression of β-APP in hippocampus.-
Key words:
- resvertrol /
- Alzheimer's disease /
- Morris water maze /
- -amyloid precursor protein
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