摘 要：目的 研究柚皮素对阿尔茨海默病（AD）模型大鼠认知水平的影响及对其β淀粉样蛋白（Aβ）和Tau抗体的调节作用，探讨其改善AD认知能力的可能机制。方法 于实验第1、3天向大鼠侧脑室内注射（icv）链脲佐菌素（STZ）建立AD模型，ig给予柚皮素、罗格列酮，模型组和对照组则ig等量生理盐水，第1次术后21 d用Morris水迷宫检测动物的学习和记忆水平；采用Western blotting检测胰岛素降解酶（insulin-degrading enzyme，IDE），糖原合成酶激酶-3β（glycogen synthase kinese-3β，GSK-3β）、磷酸化糖原合成酶激酶-3β（pGSK-3β）、Tau、磷酸化Tau（pTau）的表达；采用免疫组化检测Aβ40和Aβ42在大脑的沉积。结果 Morris水迷宫结果显示柚皮素和罗格列酮均可以恢复AD动物的认知能力（P＜0.05）；Western blotting结果显示柚皮素和罗格列酮能增加IDE的表达和降低GSK-3β的活性，减少Tau的磷酸化水平（P＜0.05）；免疫组化结果显示柚皮素和罗格列酮处理大鼠的大脑皮质Aβ40和Aβ42均减少。结论 柚皮素作为过氧化物酶体增殖因子活化受体γ（PPARγ）激动剂可以发挥胰岛素增敏剂的作用，可能通过改善与胰岛素相关的IDE和GSK-3β的表达来缓解AD动物的认知能力、Aβ的沉积和Tau的磷酸化。

Abstract: Objective To investigate the effect of naringein on the cognition of rats with Alzheimer’s diseases (AD), its regulation on amyloid β-protein (Aβ) and Tau antibody, and its potential mechanism of improving the cognition of rats with AD. Methods AD model of rats was established by intracerebroventricular (icv) Streptozotocin (STZ) on days 1 and 3, and then naringein and Rosiglitazone were ig administered. Rats in model and control groups were treated with the same volume of physiologic saline to induce dementia model. On day 21 after the first operation, spatial learning and memory of rats were tested in Morris water maze. The expression of insulin-degrading enzyme (IDE), glycogen synthase kinese-3β (GSK-3β), phospho-GSK-3β (pGSK-3β), Tau, and phospho-Tau (pTau) were measured by Western blotting. Aβ42 and Aβ40 levels in the brain of the AD rats were tested by immunohistochemistry. Results Cognition of AD rats administered with naringein and Rosiglitazone could be recovered by Morris water maze (P < 0.05). Western blotting results showed that both naringein and Rosiglitazone could improve the expression of IDE and decrease the activity of GSK-3β, and reduce the phosphorylation level of Tau (P < 0.05). Immunohistochemistry demonstrated that the Aβ42 and Aβ40 in cerebral cortex of rats treated by naringein and Rosiglitazone were both decreased. Conclusion Naringein as a peroxisome proliferator-activated receptor γ (PPARγ) excitomotor could act as insulin sensitizer, and could alleviate the cognition of AD rats, Aβ deposition, and phosphorylation of Tau through regulating the expression of insuline-related IDE and GSK-3β.