[关键词]
[摘要]
目的 研究调心方 (HBR)对杏仁核注射 β-淀粉样蛋白 (Aβ2 5- 35)致阿尔茨海默病 (AD)模型大鼠相关病理变化的作用。方法 单侧杏仁核注射 Aβ2 5- 35造成 AD大鼠模型 ,采用 Morris水迷宫法、放射免疫法、免疫组化法、RT- PCR法 ,以 Aricept为对照 ,观察 HBR对 AD模型大鼠的空间学习记忆能力、胆碱能系统、Aβ1 - 40 沉积、tau蛋白异常磷酸化及脑额叶皮层内 APP m RNA表达的影响。结果 HBR可显著改善 Aβ2 5- 35诱导的 AD大鼠空间学习记忆障碍 ,提高模型大鼠的胆碱乙酰化转移酶 (Ch AT)活性及 M受体结合容量 (Rt)值 ,减少 APP m RNA的表达和 Aβ1 - 40 的沉积 ,抑制 tau蛋白的异常磷酸化。结论 HBR对 Aβ2 5- 35诱导的 AD大鼠空间学习记忆障碍及胆碱能系统损害具有显著改善作用 ,可以明显减轻 Aβ1 - 40 的沉积和 tau蛋白的异常磷酸化。
[Key word]
[Abstract]
Object To investigate the effects of Heart-benefitting Recipe (HBR) on the histopathological changes of Alzheimer's disease (AD) rats after unilateral amyloid-β(25-35) protein Aβ(25-35) injection into the amygdala. Methods The experimental rat models with dementia,spatial learning,and memory impairment were induced by unilateral amyloid β(25-35) protein (Aβ(25-35) ) injection into the amygdala of rats. The spatial learning and memory ability and the function of cholinergic system were observed by the means of Morris water maze and radioligand binding assay. The protein expression of Aβ1-40 ,AT8 was estimated with immunohistochemistry. The expression of mRNA related to APP was observed by RT-PCR. Results HBR significantly alleviated the spatial learning and memory impairment induced by Aβ(25-35) and remarkably increased the activity of ChAT and Rt of M-receptor binding sites of these models. The expressions of Aβ1-40 protein and APP mRNA in cortex and hippocampus of AD rats were decreased remarkably by HBR. The results of immunohistochemistry showed that the expression of hyperphosphorilated tau AT8 in cortex and hippocampus of AD rats was inhibited significantly by HBR. Conclusion HBR can effectively improve the spatial learning and memory impairment,decrease the deposition of Aβ1-40 ,and alleviate the hyperphos-phorylation of tau of AD rats induced by Aβ(25-35) .
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[基金项目]
国家自然科学基金重点项目(39830450)