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发现美洲商陆和菖蒲可改善糖尿病大鼠认知功能障碍的海马蛋白。

Hippocampal proteins discovery of Panax quinquefolius and Acorus gramineus ameliorating cognitive impairment in diabetic rats.

机构信息

College of Pharmacy, Harbin University of Commerce, 138 Tongda Road, Harbin, 150076, China.

出版信息

Psychopharmacology (Berl). 2023 Aug;240(8):1759-1773. doi: 10.1007/s00213-023-06393-9. Epub 2023 Jun 12.

Abstract

RATIONALE

Early diagnosis of diabetic cognitive impairment (DCI) and investigation of effective medicines are significant to prevent or delay the occurrence of irreversible dementia.

OBJECTIVES

In this study, proteomics was applied to investigate the changes of hippocampal proteins after administration of Panax quinquefolius-Acorus gramineus (PQ-AG) to DCI rats, with a view to discover the differentially expressed proteins of PQ-AG action and elucidated the potential biological relationships.

METHODS

The model and PQ-AG group rats were injected intraperitoneally with streptozotocin, and the PQ-AG group rats were continuously administered with PQ-AG. Social interaction and Morris water maze were performed to evaluate the behavior of rats on the 17th week after the model was established, and DCI rats were screened out from the model group by a screening approach. The hippocampal protein differences were investigated with proteomics in DCI and PQ-AG-treated rats.

RESULTS

The learning and memory abilities and contact duration of DCI rats were improved after 16 weeks of PQ-AG administration. Altogether, 9 and 17 differentially expressed proteins were observed in control versus DCI rats and in DCI versus PQ-AG-treated rats, respectively. Three proteins were confirmed with western blotting analyses. These proteins were mainly involved in the pathways of JAK-STAT, apoptosis, PI3K/AKT, fork-head box protein O3, fructose, and mannose metabolism.

CONCLUSIONS

This suggested that PQ-AG ameliorated cognitive impairment of diabetic rats by influencing the above pathways and providing an experimental basis for the mechanism of DCI and PQ-AG.

摘要

背景

早期诊断糖尿病认知功能障碍(DCI)并寻找有效的治疗药物对于预防或延缓不可逆性痴呆的发生具有重要意义。

目的

本研究应用蛋白质组学方法探讨西洋参-菖蒲(PQ-AG)干预 DCI 大鼠海马蛋白质组的变化,以期发现 PQ-AG 作用的差异表达蛋白,并对其潜在的生物学关系进行阐释。

方法

采用腹腔注射链脲佐菌素(STZ)建立 DCI 大鼠模型,PQ-AG 组大鼠连续给予 PQ-AG 灌胃。于造模后第 17 周进行社交互动实验和 Morris 水迷宫实验,评价大鼠行为学改变,通过筛选方法从模型组中筛选出 DCI 大鼠。采用蛋白质组学方法观察 DCI 大鼠和 PQ-AG 干预大鼠海马蛋白质组差异。

结果

PQ-AG 干预 16 周后,DCI 大鼠的学习记忆能力和接触时间得到改善。与 DCI 大鼠相比,对照组和 PQ-AG 治疗组大鼠分别有 9 个和 17 个差异表达蛋白,经 Western blot 验证了其中 3 个蛋白。这些蛋白主要涉及 JAK-STAT、细胞凋亡、PI3K/AKT、叉头框蛋白 O3、果糖和甘露糖代谢等通路。

结论

本研究提示 PQ-AG 通过影响上述通路改善糖尿病大鼠认知功能障碍,为 DCI 及 PQ-AG 的作用机制提供了实验依据。

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