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当归龙荟丸对脑缺血再灌注损伤大鼠模型的保护作用及其机制。

Involvement of apoptosis in the protective effects of Dracocephalum moldavaica in cerebral ischemia reperfusion rat model.

机构信息

Department of Human Anatomy, Baotou Medical College, Inner Mongolia, China.

School of Health Sciences, University of Newcastle, Newcastle, Australia.

出版信息

J Toxicol Environ Health A. 2019;82(19):1036-1044. doi: 10.1080/15287394.2019.1684707. Epub 2019 Nov 18.

Abstract

An extract of (DML) was found to exert protective effects on cerebral ischemia-reperfusion injury (CIRI); however, the mechanisms underlying the observed actions of this plant-derived mixture remain to be determined. Thus, the aim of this study was to examine the influence of DML on CIRI rat model induced by middle cerebral artery occlusion (MCAO). The following parameters were measured: (1) viable neurons in the infarcted area using Nissl staining; and (2) immunohistochemistry and Western blot were employed to determine protein expression levels of p53, bcl-2 associated X protein (bax) and B-cell lymphoma-2 (bcl-2), three biomarkers of apoptosis. MCAO significantly decreased the number of viable cortical pyramidal neurons in the infarcted area, while treatment with DML extract significantly elevated the number of viable neurons. MCAO was found to significantly elevate in gene expression levels of p53 and protein expression levels bax accompanied by diminished protein expression levels of bcl-2. Prior administration of DML extract produced marked reduction in gene expression levels of p53 and protein expression levels bax but increased in protein expression levels of bcl-2. Data suggested apoptosis was initiated in MCAO and that DML was effective in treating CIRI via an anti-apoptotic action as evidenced by inhibition of gene expression levels of p53 and protein expression levels of bax with concomitant elevation in protein expression levels of bcl-2. Our findings suggest that extract of DML may prove beneficial in treatment of cerebrovascular disorders.

摘要

(DML) 的提取物被发现对脑缺血再灌注损伤 (CIRI) 具有保护作用;然而,这种植物源性混合物观察到的作用的机制仍有待确定。因此,本研究旨在研究 DML 对大脑中动脉闭塞 (MCAO) 诱导的 CIRI 大鼠模型的影响。测量了以下参数:(1) 用尼氏染色检测梗死区存活神经元;(2) 免疫组织化学和 Western blot 用于测定 p53、bcl-2 相关 X 蛋白 (bax) 和 B 细胞淋巴瘤-2 (bcl-2) 的蛋白表达水平,这三种凋亡生物标志物。MCAO 显著降低了梗死区皮质锥体神经元的数量,而 DML 提取物处理显著增加了存活神经元的数量。发现 MCAO 显著增加了 p53 的基因表达水平和 bax 的蛋白表达水平,同时 bcl-2 的蛋白表达水平降低。DML 提取物的预先给药导致 p53 的基因表达水平和 bax 的蛋白表达水平显著降低,但 bcl-2 的蛋白表达水平升高。数据表明,MCAO 中启动了细胞凋亡,DML 通过抑制 p53 的基因表达水平和 bax 的蛋白表达水平,同时升高 bcl-2 的蛋白表达水平,从而有效治疗 CIRI,发挥抗凋亡作用。我们的研究结果表明,DML 提取物可能对治疗脑血管疾病有益。

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