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评价橙皮素负载于多壁碳纳米管对大鼠脑缺血/再灌注损伤的作用。

Evaluation of hesperetin-loaded on multiple wall carbon nanotubes on cerebral ischemia/reperfusion injury in rats.

机构信息

Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

出版信息

Biomed Pharmacother. 2021 Jun;138:111467. doi: 10.1016/j.biopha.2021.111467. Epub 2021 Mar 16.

Abstract

The present study aimed to develop novel hesperetin-loaded on multiple wall carbon nanotubes (Hst-MWCNTs) to resolve the restricted bioavailability of hesperetin (Hst) and to enhance its preventive effect on cerebral ischemia-reperfusion (I/R). The physicochemical characteristics of Hst-MWCNTs were evaluated by Fourier-transform infrared spectra (FT-IR) and field emission scanning electron microscopy (FE-SEM). Forty male Wistar rats were randomly divided into five groups (control, I/R, MWCNTs, Hst, and Hst-MWCNTs). Hst, MWCNTs and Hst-MWCNTs (15 mg/kg orally) were pretreated for 14 days, and then I/R was induced by bilateral common carotid artery occlusion (BCCAO). Learning and memory deficits were evaluated using the novel object recognition test (NORT). The percentage of infarct size, catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GRx), glutathione peroxidase (GPx) activities, malondialdehyde (MDA), and glutathione (GSH) levels was evaluated. Caspase-3 and Bcl-2 expressions were detected by qRT-PCR and Western blot analysis. Compared to the I/R group, Hst-MWCNTs considerably reduced learning and memory deficits, infarct size, and MDA levels. CAT, SOD, GRx, GPx activities and GSH levels were significantly increased in the Hst-MWCNTs group than in the I/R group. Additionally, Hst-MWCNTs significantly reduced the Caspase-3 expression but increased the Bcl-2 expression. All these results indicated that MWCNTs could be used as a promising novel carrier to enhance the oral bioavailability of Hst and to treat cerebral I/R injury.

摘要

本研究旨在开发新型橙皮素负载于多壁碳纳米管(Hst-MWCNTs),以解决橙皮素(Hst)的生物利用度受限问题,并增强其对脑缺血再灌注(I/R)的预防作用。通过傅里叶变换红外光谱(FT-IR)和场发射扫描电子显微镜(FE-SEM)对 Hst-MWCNTs 的物理化学性质进行了评价。将 40 只雄性 Wistar 大鼠随机分为 5 组(对照组、I/R 组、MWCNTs 组、Hst 组和 Hst-MWCNTs 组)。Hst、MWCNTs 和 Hst-MWCNTs(15mg/kg 口服)预处理 14 天,然后通过双侧颈总动脉闭塞(BCCAO)诱导 I/R。使用新物体识别试验(NORT)评估学习和记忆缺陷。评估梗死面积百分比、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GRx)、谷胱甘肽过氧化物酶(GPx)活性、丙二醛(MDA)和谷胱甘肽(GSH)水平。通过 qRT-PCR 和 Western blot 分析检测 caspase-3 和 Bcl-2 的表达。与 I/R 组相比,Hst-MWCNTs 显著降低了学习和记忆缺陷、梗死面积和 MDA 水平。Hst-MWCNTs 组的 CAT、SOD、GRx、GPx 活性和 GSH 水平明显高于 I/R 组。此外,Hst-MWCNTs 显著降低了 caspase-3 的表达,增加了 Bcl-2 的表达。所有这些结果表明,MWCNTs 可用作一种有前途的新型载体,以提高 Hst 的口服生物利用度并治疗脑 I/R 损伤。

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