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积雪草苷通过抑制线粒体凋亡和减少炎症因子来改善β-淀粉样蛋白诱导的大鼠学习和记忆缺陷。

Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors.

作者信息

Zhang Zhuo, Li Xiaobin, Li Duo, Luo Mao, Li Yongjie, Song Li, Jiang Xian

机构信息

Department of Pharmacology, Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.

Department of Respiratory Internal Medicine, The First Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.

出版信息

Exp Ther Med. 2017 Feb;13(2):413-420. doi: 10.3892/etm.2016.4004. Epub 2016 Dec 27.

Abstract

The present study aimed to investigate the effects of asiaticoside (AS) on the pathology and associated mechanisms of β-amyloid (Aβ)-induced Alzheimer's disease (AD) in rats. An AD rat model was established by lateral intracerebroventricular injection of Aβ 1-42 oligomers. Learning and memory function were evaluated by Morris water maze (MWM) test. In addition, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunohistochemistry, ELISA and western blot analysis were performed to evaluate the disease pathogenesis. The results indicated that AS exerted protective effects in rats treated with Aβ oligomers, in a dose-dependent manner, as evidenced by the improved learning and memory function in the MWM test. In addition, H&E staining of hippocampal tissue showed that the histological structure was damaged in the model group, which was restored by AS treatment. Aβ deposition was dramatically increased in the model group, and the pathological changes were reversed by AS treatment. TEM revealed that the subcellular structure was injured by Aβ oligomers, however, the structure was ameliorated by AS treatment. Furthermore, AS was found to reduce the elevated levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in the brains of Aβ-treated rats. In addition, AS treatment resulted in a significant decrease in the expression of caspases-3, whereas the expression of B-cell lymphoma-2 was significantly increased, in these Aβ-treated rats. According to the findings of the observed study, AS has a marked protective effect on Aβ-induced AD pathology, and the underlying mechanism may be associated with the alleviation of the mitochondrial injuries, the anti-inflammatory activities, and the influence on the expression levels of apoptosis-associated proteins.

摘要

本研究旨在探讨积雪草苷(AS)对β-淀粉样蛋白(Aβ)诱导的大鼠阿尔茨海默病(AD)病理学及相关机制的影响。通过侧脑室注射Aβ 1-42寡聚体建立AD大鼠模型。采用莫里斯水迷宫(MWM)试验评估学习和记忆功能。此外,进行苏木精-伊红(H&E)染色、透射电子显微镜(TEM)、免疫组织化学、酶联免疫吸附测定(ELISA)和蛋白质免疫印迹分析以评估疾病发病机制。结果表明,AS对用Aβ寡聚体处理的大鼠具有保护作用,且呈剂量依赖性,MWM试验中学习和记忆功能的改善证明了这一点。此外,海马组织的H&E染色显示模型组的组织结构受损,而AS处理可使其恢复。模型组Aβ沉积显著增加,AS处理可逆转病理变化。TEM显示亚细胞结构受到Aβ寡聚体的损伤,然而,AS处理可改善该结构。此外,发现AS可降低Aβ处理大鼠脑中促炎细胞因子白细胞介素-6和肿瘤坏死因子-α的升高水平。此外,在这些Aβ处理的大鼠中,AS处理导致半胱天冬酶-3的表达显著降低,而B细胞淋巴瘤-2的表达显著增加。根据观察性研究的结果,AS对Aβ诱导的AD病理学具有显著的保护作用,其潜在机制可能与减轻线粒体损伤、抗炎活性以及对凋亡相关蛋白表达水平的影响有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e26/5348711/500b53696ee3/etm-13-02-0413-g00.jpg

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