摘要
目的观察阿托伐他汀对Aβ1-40诱导AD大鼠模型的保护作用,探讨其可能机制。方法雄性SD大鼠40只,体质量250～300g,随机分为空白对照组、假手术组、Aβ组、Aβ+生理盐水组、Aβ+阿托伐他汀组,每组8只。后3组在大鼠双侧海马CA1区立体定向注射Aβ造AD模型,假手术组注射生理盐水,正常对照组不作任何处理。Aβ+阿托伐他汀组在造模1周前开始给予阿托伐他汀20mg.kg-1.d-1灌胃,Aβ+生理盐水组给予等量生理盐水灌胃。造模4周后,采用Morris水迷宫衡量大鼠学习记忆水平;测定大鼠脑皮质、海马组织AchE、ChAT活性的变化;蛋白印迹技术检测大鼠海马区GFAP的表达。结果与空白对照组相比,Aβ组大鼠的学习记忆能力明显下降(P<0.05);脑皮质、海马组织内AchE活性明显升高(P<0.05),ChAT活性明显降低(P<0.05),GFAP的表达升高(P<0.05),与Aβ组相比,Aβ+阿托伐他汀组大鼠的学习记忆能力明显提高(P<0.05);大脑皮质、海马组织内AchE明显减低(P<0.05),ChAT活性明显升高(P<0.05),GFAP的表达下降(P<0.05)。结论阿托伐他汀Aβ1-40诱导AD大鼠模型的学习记忆能力有明显提高,其作用机制与抑制AchE和GFAP活性、提高ChAT活性有关。
Objective To investigate the effect of atorvastatin on Alzheimer＇s disease rat model induced by Aβ140. Methods Forty healthy Wistar rats were randomly divided into 5 groups： Aβ group, Aβ＋atorvastatin group, Aβ＋NS group, shamoperation group and nomal control group. The first 3 groups were given Aβ to induce AD model, sham-operation group was given normal saline, and then Aβ＋atorvastatin group and Aβ q-NS group were given to have corresponding drugs, respcetively. After 4 weeks, the Morris water maze （MWM） was used to test the spatial learning and memory performance,and the activity of Ache andChAT in the cortex and hippocampus were measured. At the same time, the expression level of GFAP was detected by using Western blot. Results The MWM test showed that the model group rats had significant memory impairment compared with the control group （P〈0.05）. In the cortex and hippocampus of the model group rats, the expression level of ChAT significantly decreased （P〈0.05）compared with the control group. Atorvastatin treatment could inhibit the memory impairment, decrease the expression levels of AchE and GFAP,and increase the expression level of ChAT in AD rat model （P〈 0.05）. Conclusion Atorvastatin has a neuroprotective effect on AD by increasing the expression level of ChAT and decreasing the expression levels of Ache and GFAP.
出处
《中国实用神经疾病杂志》
2013年第12期6-9,共4页
Chinese Journal of Practical Nervous Diseases
