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生育三烯酚预处理对缺血后小鼠脑氧化应激的治疗作用。

Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain.

作者信息

Shang Jingwei, Yan Hongjing, Jiao Yang, Ohta Yasuyuki, Liu Xia, Li Xianghong, Morihara Ryuta, Nakano Yumiko, Fukui Yusuke, Shi Xiaowen, Huang Yong, Feng Tian, Takemoto Mami, Sato Kota, Hishikawa Nozomi, Yamashita Toru, Abe Koji

机构信息

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kitaku, Okayama, Japan.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kitaku, Okayama, Japan.

出版信息

J Stroke Cerebrovasc Dis. 2018 Aug;27(8):2096-2105. doi: 10.1016/j.jstrokecerebrovasdis.2018.03.012. Epub 2018 May 21.

Abstract

BACKGROUND

Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice.

MATERIALS AND METHODS

After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice.

RESULTS

We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO.

CONCLUSIONS

The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

摘要

背景

膳食补充剂旨在降低高危人群缺血性中风的风险。一种主要含生育三烯酚而非生育酚的新型混合维生素E-Tocovid,通过口服可减缓人体白质病变的进展。然而,Tocovid对缺血性中风的影响尚未得到研究。在本研究中,我们评估了Tocovid预处理对小鼠短暂性大脑中动脉闭塞(tMCAO)的治疗效果。

材料与方法

用Tocovid(200mg/kg/d)或赋形剂预处理1个月后,进行60分钟的tMCAO,然后在再灌注后1天、3天和7天对这些小鼠进行检查。我们通过组织学评估了Tocovid预处理对tMCAO后小鼠氧化应激标志物、裂解的半胱天冬酶-3和LC3-II表达变化的影响。

结果

我们观察到,Tocovid预处理显著改善了转棒试验时间,减少了梗死体积,减少了4-HNE、硝基酪氨酸和8-OhdG阳性细胞的数量,抑制了晚期糖基化终产物生物标志物RAGE、CMA和CML的表达,并增加了Nrf2和MRP1水平,同时GSSG/GSH比值降低。此外,Tocovid预处理大大降低了tMCAO后裂解的半胱天冬酶-3和LC3-II的表达。

结论

本研究明显表明,Tocovid预处理对缺血小鼠脑的氧化应激具有神经保护作用,且至少部分是通过抗凋亡/自噬性细胞死亡实现的。

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