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白杨素通过调节 PI3K/Akt/mTOR 通路改善大鼠脑缺血再灌注(I/R)损伤。

Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway.

机构信息

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou, 450052, PR China.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou, 450052, PR China.

出版信息

Neurochem Int. 2019 Oct;129:104496. doi: 10.1016/j.neuint.2019.104496. Epub 2019 Jun 25.

DOI:10.1016/j.neuint.2019.104496
PMID:31247243
Abstract

In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTOR pathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.

摘要

在这项研究中,通过建立大鼠大脑中动脉闭塞(MCAO)模型,研究了白杨素对脑缺血的影响。在体内实验中,大鼠在缺血实验前每天口服给予氯吡格雷或白杨素一次,连续 7 天,然后将大鼠分为 5 组:假手术组、缺血再灌注组、缺血再灌注+氯吡格雷组、缺血再灌注+白杨素(10mg/kg)组、缺血再灌注+白杨素(20mg/kg)组。通过 TTC 染色、脑湿重/干重比测定和神经功能缺损评分评估,白杨素显著改善了 I/R 大鼠的状况。此外,在 I/R 大鼠的血清和脑组织中,白杨素还能有效抑制炎症细胞因子的释放,包括白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的水平。此外,白杨素还能提高 I/R 大鼠的 SOD 活性。在体外氧葡萄糖剥夺和复氧(OGD/R)诱导的 SH-SY5Y 细胞中,白杨素通过激活 PI3K/Akt/mTOR 通路,抑制炎症和细胞凋亡,显著降低了 OGD/R 诱导的 SH-SY5Y 细胞上清液中 TNF-α、IL-6 和 IL-1β的水平。综上所述,本研究表明白杨素可能是一种治疗脑缺血的潜在药物。

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