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基于 PI3K/Akt 信号通路研究山葡萄花色苷改善毒死蜱诱导的认知障碍。

Improvement of chlorpyrifos-induced cognitive impairment by mountain grape anthocyanins based on PI3K/Akt signaling pathway.

机构信息

College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China.

Jilin Province Product Quality Supervision and Inspection Institute of Light Industrial and Chemical Products Inspection, Changchun 130022, China.

出版信息

Pestic Biochem Physiol. 2024 Nov;205:106172. doi: 10.1016/j.pestbp.2024.106172. Epub 2024 Oct 15.

Abstract

The organophosphorus insecticide Chlorpyrifos (CPF) is widely used worldwide due to its high effectiveness. However, when ingested through the mouth and nose, it can cause severe neurotoxic effects and cognitive impairment. Natural anthocyanins show great potential in improving cognitive impairment. In this paper, we will delve into the protective effect of anthocyanins on CPF-induced cognitive impairment and its mechanism through the PI3K/Akt signaling pathway. Morris water maze, histopathological, ELISA and western blot analyses showed that anthocyanins effectively ameliorated CPF-induced spatial learning memory impairment in mice by ameliorating CPF-induced AChE inhibition, oxidative stress, and neuroinflammation and by modulating the levels of apoptosis (Caspase-3, Caspase-9) and autophagy (LC3II/ LC3I, Beclin1, p62, mTOR) biomarkers, in order to restore damaged hippocampal tissue morphology, neuron and synapse structures. To identify the action pathway of anthocyanins, we used KEGG and GO pathway enrichment analysis for screening prediction and western blot and molecular docking to verify that anthocyanins improve CPF-induced cognitive impairment by activating the PI3K/Akt pathway.

摘要

有机磷杀虫剂毒死蜱(CPF)由于其高效性而在世界范围内广泛使用。然而,当通过口腔和鼻腔摄入时,它会引起严重的神经毒性作用和认知障碍。天然花色苷在改善认知障碍方面显示出巨大的潜力。在本文中,我们将深入研究花色苷通过 PI3K/Akt 信号通路对 CPF 诱导的认知障碍的保护作用及其机制。Morris 水迷宫、组织病理学、ELISA 和 Western blot 分析表明,花色苷通过改善 CPF 诱导的乙酰胆碱酯酶抑制、氧化应激和神经炎症,以及调节凋亡(Caspase-3、Caspase-9)和自噬(LC3II/LC3I、Beclin1、p62、mTOR)生物标志物的水平,有效改善了 CPF 诱导的小鼠空间学习记忆障碍,从而恢复受损的海马组织形态、神经元和突触结构。为了确定花色苷的作用途径,我们使用 KEGG 和 GO 通路富集分析进行筛选预测,并用 Western blot 和分子对接进行验证,表明花色苷通过激活 PI3K/Akt 通路改善 CPF 诱导的认知障碍。

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