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西红花通过抑制星形胶质细胞增生和胶质瘢痕形成对大鼠迟发性脑缺血损伤的神经保护作用。

Neuroprotective effects of saffron on the late cerebral ischemia injury through inhibiting astrogliosis and glial scar formation in rats.

机构信息

School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Huzhou Central Hospital, Huzhou, Zhejiang, China.

出版信息

Biomed Pharmacother. 2020 Jun;126:110041. doi: 10.1016/j.biopha.2020.110041. Epub 2020 Feb 26.

Abstract

This study is to explore the neuroprotective effects and involved glial scar of saffron (Crocus sativus L.) on the late cerebral ischemia in rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats that were randomly divided into sham group, MCAO group, edaravone group (as a positive control) and saffron groups (saffron extract 30, 100, 300 mg/kg). Saffron was administered orally at 2 h at the first day and once daily from day 2 to 42 after ischemia. Behavioral changes were detected from day 43 to 46 after ischemia to evaluate the effects of saffron. Infarct volume, survival neuron density, activated astrocyte, and the thickness of glial scar were also detected. GFAP, neurocan, phosphocan, neurofilament expressions and inflammatory cytokine contents were detected by Western-blotting and ELISA methods, respectively. Saffron improved the body weight loss, neurological deficit and spontaneous activity. It also ameliorated anxiety-like state and cognitive dysfunction, which were detected by elevated plus maze (EPM), marble burying test (MBT) and novel object recognition test (NORT). Toluidine blue staining found that saffron treatment decreased the infarct volume and increased the neuron density in cortex in the ischemic boundary zone. The activated astrocyte number and the thickness of glial scar in the penumbra zone reduced after saffron treatment. Additionally, saffron decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in the ischemic boundary zone. GFAP, neurocan, and phosphocan expressions in ischemic boundary zone and ischemic core zone all decreased after saffron treatment. Saffron exerted neuroprotective effects on late cerebral ischemia, associating with attenuating astrogliosis and glial scar formation after ischemic injury.

摘要

本研究旨在探讨藏红花(Crocus sativus L.)对大鼠迟发性脑缺血的神经保护作用及其涉及的神经胶质瘢痕。采用大脑中动脉闭塞(MCAO)法诱导 Sprague Dawley 大鼠局灶性脑缺血,将大鼠随机分为假手术组、MCAO 组、依达拉奉组(阳性对照)和藏红花组(藏红花提取物 30、100、300 mg/kg)。藏红花于第一天缺血后 2 小时开始口服给药,每天一次,连续给药 42 天。在缺血后 43 天至 46 天检测行为变化,以评估藏红花的作用。还检测了梗塞体积、存活神经元密度、激活的星形胶质细胞和神经胶质瘢痕的厚度。通过 Western-blotting 和 ELISA 方法检测 GFAP、神经粘蛋白、磷酸神经粘蛋白、神经丝表达和炎症细胞因子含量。藏红花改善了体重减轻、神经功能缺损和自发性活动。它还改善了焦虑样状态和认知功能障碍,这是通过高架十字迷宫(EPM)、大理石掩埋试验(MBT)和新物体识别试验(NORT)检测到的。甲苯胺蓝染色发现,藏红花治疗减少了梗塞体积,并增加了缺血边界区皮质中的神经元密度。藏红花治疗后,半影区激活的星形胶质细胞数量和神经胶质瘢痕的厚度减少。此外,藏红花降低了缺血边界区 IL-6 和 IL-1β 的含量,增加了 IL-10 的含量。藏红花治疗后,缺血边界区和缺血核心区的 GFAP、神经粘蛋白和磷酸神经粘蛋白表达均降低。藏红花对迟发性脑缺血具有神经保护作用,与减轻缺血损伤后星形胶质细胞增生和神经胶质瘢痕形成有关。

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