Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways.
Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways.
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DOI：
10.3390/molecules23092401
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发表时间：
2018-09-19
期刊：
影响因子：
--
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Meng X;Xie W;Xu Q;Liang T;Xu X;Sun G;Sun X
缺血性脑卒中是临床常见的脑血管病，其主要危险因素包括脑缺血再灌注（I/R）引起的坏死、凋亡和脑梗死。脑缺血再灌注损伤或凋亡抑制对缺血神经可能具有不可替代的保护作用。这一过程对中风患者的治疗具有特别重要的意义。然而，神经保护药物的开发仍然具有挑战性。玄参是一种名贵中药，具有神经保护作用。为探讨玄参水提物（RSAE）对脑缺血/再灌注损伤的保护作用及其机制，采用缺氧缺糖再灌注（OGD/R）诱导的PC 12细胞，建立小鼠大脑中动脉闭塞/再灌注（MCAO/R）模型。体外实验结果表明，12.5 μg/mLRSAE能显著提高细胞活力，抑制LDH漏出，提高SOD、GSH-Px和CAT酶活性，稳定线粒体膜电位，减少OGD诱导的细胞损伤和凋亡。此外，体内实验结果初步表明，RSAE可缩小MCAO/R模型小鼠的梗死体积，降低脑含水量、一氧化氮（NO）和丙二醛（MDA）含量，抑制I/R所致的神经功能缺损，减少乳酸脱氢酶（LDH）漏出，通过上调SOD、GSH-Px和CAT酶活性提高抗氧化能力，并减少神经元凋亡、坏死和神经元丢失。RSAE可上调Bcl-2的表达，下调Bax的表达。此外，MAPK信号通路的磷酸化水平通过蛋白质印迹分析和免疫组织化学评价来阐明。本研究探讨了RSAE对小鼠局灶性脑I/R损伤的神经保护作用及其可能机制。玄参是一种具有神经保护作用的天然植物。因此，我们的研究结果可能为发现新的活性化合物或药物用于治疗缺血性中风提供见解。通过化学分离和鉴定，可能会发现该提取物中许多新的天然活性化学物质，并可能为中风患者的治疗靶点提供新的见解。
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on ischemic nerves. This process has particular significance for the treatment of stroke patients. However, the development of neuroprotective drugs remains challenging. Radix Scrophulariae, traditionally considered a valuable medicine, has been discovered to have neuroprotective effects. To explore the neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In vitro results showed that 12.5 μg/mL RSAE markedly improved cell viability; inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized the mitochondrial membrane potential; and reduced OGD-induced cell injury and apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R model mice, RSAE treatments attenuated infarct volume; reduced brain water content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and downregulated the expression of Bax. In addition, the phosphorylation levels of MAPK signal pathways were elucidated via western blot analysis and immunohistochemical evaluation. In summary, this study investigated the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Radix Scrophulariae has been previously identified as a potential neuroprotective natural plant. Hence, our results may offer insight into discovering new active compounds or drugs for the treatment of ischemic stroke. Many new natural active chemicals in this extract may be discovered by chemical separation and identification and may provide new insights into therapeutic targets in stroke patients.
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影响因子：
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通讯作者：
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