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曲马多给药对成年大鼠海马细胞凋亡、学习和记忆的影响及西红花酸的神经保护作用。

The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin.

机构信息

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Azadi Sq., Vakilabad Blvd, P.O. Box 91779-48564, Mashhad, Iran.

Microanatomy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Metab Brain Dis. 2018 Jun;33(3):907-916. doi: 10.1007/s11011-018-0194-6. Epub 2018 Feb 22.

DOI:10.1007/s11011-018-0194-6
PMID:29470767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5956046/
Abstract

Tramadol, a frequently used pain reliever drug, present neurotoxic effects associated to cognitive dysfunction. Moreover, crocin has been reported to have neuroprotective effects. The aim of this study was to assess crocin's capacity to protect learning, and memory abilities on tramadol-treated rats. A total of 35 rats were divided into five groups: Control, Saline, tramadol (50 mg/kg), tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive days. Morris water maze (MWM) and passive avoidance (PA) tests were done, followed by dissection of the rat's brains for toluidine blue and TUNEL staining. In MWM test, tramadol group spent lower time and traveled shorter distance in the target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the delay for entering the dark, and the total time spent in the light compartment decreased in tramadol comparing to the control group (P < 0.05), while it increased in tramadol-crocin compared with the tramadol group (P < 0.05). In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to improve learning and memory of tramadol-treated rats and also decreased DNs and apoptotic cells in the hippocampus. Considering these results, the potential capacity of crocin for decreasing side effects of tramadol on the nervous system is suggested.

摘要

曲马多是一种常用的止痛药,具有神经毒性作用,与认知功能障碍有关。此外,藏红花素已被报道具有神经保护作用。本研究旨在评估藏红花素对曲马多治疗大鼠学习和记忆能力的保护作用。将 35 只大鼠分为 5 组:对照组、生理盐水组、曲马多(50mg/kg)组、曲马多+藏红花素(30mg/kg)组和藏红花素组,连续口服 28 天。进行 Morris 水迷宫(MWM)和被动回避(PA)测试,然后对大鼠大脑进行甲苯胺蓝和 TUNEL 染色。在 MWM 测试中,曲马多组在目标象限(Q1)花费的时间更少,行驶的距离更短(P<0.05)。另一方面,曲马多-藏红花素组的行驶距离高于曲马多组(P<0.05)。在 PA 测试中,与对照组相比,曲马多组进入黑暗的延迟时间和在亮室停留的总时间减少(P<0.05),而曲马多-藏红花素组与曲马多组相比则增加(P<0.05)。在曲马多处理的动物中,CA1、CA3 和 DG 中的暗神经元(DNs)和凋亡细胞增加(P<0.05),而同时摄入藏红花素可减少这些区域的 DNs 和凋亡细胞数量(P<0.05)。藏红花素能改善曲马多治疗大鼠的学习和记忆能力,并减少海马区的 DNs 和凋亡细胞。考虑到这些结果,提示藏红花素具有降低曲马多对神经系统副作用的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/103f097288e5/11011_2018_194_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/592f34d54c8d/11011_2018_194_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/effbb128a441/11011_2018_194_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/07f736cb9747/11011_2018_194_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/103f097288e5/11011_2018_194_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/c8db17d20098/11011_2018_194_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/700d804a6c99/11011_2018_194_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/9d04fe1e8e60/11011_2018_194_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/592f34d54c8d/11011_2018_194_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/effbb128a441/11011_2018_194_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/07f736cb9747/11011_2018_194_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f176/5956046/103f097288e5/11011_2018_194_Fig7_HTML.jpg

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