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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(glycogensynthase 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。
Objective To investigate the effect of naringenin on cognition of Alzheimer’s disease (AD) model rats and the regulation of its amyloid beta (Aβ) and Tau antibodies, and to explore the possible mechanism of naringenin in improving AD cognitive function. Methods AD rats were injected intracerebroventricular (icv) streptozotocin (STZ) on the first and the third day of experiment to establish the model of AD, ig administration of naringenin and rosiglitazone, and the model group and the control group The rats were sacrificed on the first postoperative day 21 with Morris water maze to detect the learning and memory of the animals. Western blotting was used to detect the expression of insulin-degrading enzyme (IDE), glycogensynthase kinese-3β , GSK-3β), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Tau and phosphorylated Tau (pTau) were detected by immunohistochemical method. The deposition of Aβ40 and Aβ42 in the brain was detected by immunohistochemistry. Results Morris water maze results showed that both naringenin and rosiglitazone restored the cognition ability of AD animals (P <0.05). Western blotting showed that naringenin and rosiglitazone increased the expression of IDE and decreased the expression of GSK- 3β, and decreased the phosphorylation level of Tau (P <0.05). The results of immunohistochemistry showed that both Aβ40 and Aβ42 decreased in the cerebral cortex of naringenin and rosiglitazone-treated rats. Conclusion Naringenin, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, can act as an insulin sensitizer and may alleviate AD animals’ expression by improving insulin-related expression of IDE and GSK-3β Aptitude, deposition of Aβ and phosphorylation of Tau.