作者：古长维，刘仲，武苗苗，辛红娟，党晓燕

单位：

710004 陕西省西安市，西安交通大学第二附属医院急诊科；通信作者：党晓燕，E-mail：dxiaoyan1@163.com

Units：

Department of Emergency Medicine，the Second Affiliated Hospital of Xi'an Jiaotong University，Xi'an 710004，China；Corresponding author：DANG Xiaoyan，E-mail：dxiaoyan1@163.com

关键词：

卒中；广藿香酮；血管内皮生长因子；大鼠

Keywords：

Stroke；Pogostone；Vascular endothelial growth factor；Rats

CLC：

R 743

DOI：

DOI：10.3969/j.issn.1008-5971.2020.03.016

Funds：

基金项目：陕西省重点研发计划项目（2019SF-167）

摘要：

背景　广藿香酮（POG）具有抗癌、抗炎、抗菌等多重药理作用，但目前关于其治疗脑卒中的研究报道较少。目的　探讨 POG 对脑卒中大鼠的影响及其作用机制。方法　本实验于 2018 年 12 月—2019 年 4 月完成。选取 7~8 周龄 SPF 级雄性 Sprague-Dawley 大鼠 36 只，随机分为空白对照组（未经模型诱导，n=6）、对照组（建模后未经治疗，n=6）、低剂量组（建模 24 h 后给予 POG 5 mg/kg，n=6）、中剂量组（建模 24 h 后给予 POG 15 mg/kg，n=6）、高剂量组（建模 24 h 后给予 POG 45 mg/kg，n=6）和 LY294002 组（建模 24 h 后给予 0.1%~0.3% 二甲亚砜溶解浓度为 0.1%，n=6）。比较六组大鼠磷酸化 PI3K（p-PI3K）、磷酸化 AKT（p-AKT）、磷酸化内皮型一氧化氮合酶（p-eNOS）蛋白相对表达量，血管内皮生长因子（VEGF）、B 细胞淋巴瘤 2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）蛋白及 mRNA 相对表达量，大脑皮质和外周血中的超氧化物歧化酶（SOD）、丙二醛（MDA）和一氧化氮（NO）水平。结果　（1）高剂量组大鼠 p-PI3K、p-AKT、p-eNOS 蛋白相对表达量低于对照组，p-AKT 和 p-eNOS 蛋白相对表达量高于 LY294002 组（P<0.05）。（2）高剂量组大鼠 Bcl-2 蛋白相对表达量高于对照组，Bax、VEGF 蛋白相对表达量低于对照组（P<0.05）；高剂量组大鼠 Bcl-2、VEGF mRNA 相对表达量高于对照组，Bax mRNA 相对表达量低于对照组（P<0.05）。（3）高剂量组大鼠大脑皮质和外周血 NO、SOD 水平高于对照组，大脑皮质和外周血 MDA 水平低于对照组（P<0.05）；高剂量组大鼠大脑皮质和外周血 MDA 水平高于 LY294002 组，大脑皮质和外周血 SOD 水平低于LY294002 组（P<0.05）。结论　POG 可通过抑制 PI3K/AKT-eNOS 信号通路及脂质过氧化而减轻脑卒中大鼠脑组织损伤，且无剂量依赖性。

Abstract：

Background　Pogostone（POG）has multiple pharmacological action，such as anti-cancer，anti-inflammatory and anti-bacterial effect，however，there are few reports about POG in the treatment of stroke. Objective　Toinvestigate the impact of POG on rates with stroke and its mechanism. Methods　This experiment was conducted from December2018 to April 2019. A total of 36 SPF male Sprague-Dawley rats（7 to 8 weeks old）were selected and randomly divided intoblank control group（did not prepared for stroke model，n=6），control group（did not treated after preparation of strokemodel，n=6），low-dose group（received POG by 5 mg/kg 24 hours after preparation of stroke model，n=6），middle-dosegroup（received POG by 15 mg/kg 24 hours after preparation of stroke model，n=6），high-dose group（received POG by45 mg/kg 24 hours after preparation of stroke model，n=6）and LY294002 group（received 0.1% to 0.3% dimethyl sulfoxidethat being ultimately dissolved to 0.1% 24 hours after preparation of stroke model，n=6）. Comparison was conducted in the sixgroups，involving relative protein expression quantity of p-PI3K，p-AKT and p-eNOS，relative protein and RNA expressionquantity of VEGF，Bcl-2 and Bax，as well as SOD，MDA and NO in cerebral cortex and peripheral blood. Results　（1）Relative protein expression quantity of p-PI3K，p-AKT and p-eNOS in high-dose group was statistically significantly lowerthan that in control group，respectively，while relative protein expression quantity of p-AKT and p-eNOS in high-dose groupwas statistically significantly higher than that in LY294002 group，respectively（P<0.05）.（2）Relative protein expressionquantity of Bcl-2 in high-dose group was statistically significantly higher than that in control group，relative protein expressionquantity of Bax and VEGF in high-dose group was statistically significantly lower than that in control group，respectively（P<0.05）；relative mRNA expression quantity of Bcl-2 and VEGF in high-dose group was statistically significantly higherthan that in control group，respectively，while relative mRNA expression quantity of Bax in high-dose group was statisticallysignificantly lower than that in control group（P<0.05）.（3）NO and SOD in cerebral cortex and peripheral blood in high-dosegroup was statistically significantly higher than that in control group，respectively，while MDA in cerebral cortex and peripheralblood in high-dose group was statistically significantly lower than that in control group，respectively（P<0.05）；MDA incerebral cortex and peripheral blood in high-dose group was statistically significantly higher than that in LY294002 group，respectively，while SOD in cerebral cortex and peripheral blood in high-dose group was statistically significantly higher thanthat in LY294002 group，respectively（P<0.05）. Conclusion　POG may reduce the damage of brain tissue through inhibitingPI3K/AKT-eNOS signaling pathway and lipid peroxidation in rats with stroke，without dose dependence.

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