中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (15): 1349-1359.doi: 10.3969/j.issn.1673-5374.2013.15.001

• 原著:脑损伤修复保护与再生 •    下一篇

氧化槐定碱保护脑缺血后再灌注损伤的作用相当尼莫地平

  

  • 收稿日期:2013-02-01 修回日期:2013-04-20 出版日期:2013-05-25 发布日期:2013-05-25

Protective effect of oxysophoridine on cerebral ischemia/reperfusion injury in mice

Hongbo Wang1, Yuxiang Li2, 3, Ning Jiang3, Xiaoping Chen3, Yi Zhang3, Kuai Zhang1, Tengfei Wang1, Yinju Hao1, Lin Ma4, Chengjun Zhao5, Yanrong Wang6, Tao Sun4, Jianqiang Yu1, 7   

  1. 1 Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
    2 College of Nursing, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
    3 Shanghai Pudong New Area Gongli Hospital, Shanghai 200135, China
    4 Ningxia Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Yinchuan 750004, Ningxia Hui Autonomous Region, China
    5 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
    6 Key Laboratory of Reproduction and Genetics of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
    7 Collaborative Innovation Center of Ningxia Hui Autonomous Region for Medicines, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2013-02-01 Revised:2013-04-20 Online:2013-05-25 Published:2013-05-25
  • Contact: Jianqiang Yu, Master, Professor, Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Collaborative Innovation Center of Ningxia Hui Autonomous Region for Medicines, Yinchuan 750004, Ningxia Hui Autonomous Region, China, Yujq910315@163.com.
  • About author:Hongbo Wang★, Studying for master’s degree. Hongbo Wang and Yuxiang Li contributed equally to this work.
  • Supported by:

    国家自然科学基金（No. 30960506，81160524）；宁夏自然科学基金（No. NZ11212）；宁夏回族自治区卫生厅重点科研攻关项目（No. 2012152）；宁夏医科大学面上项目（No. 2011017）

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摘要：

氧化槐定碱是从苦豆子中提取的生物碱，课题组的前期研究发现其对缺血性脑损伤有保护作用。本次实验采用线栓法阻塞小鼠大脑中动脉2 h后行再灌注制备局灶性脑缺血再灌注损伤模型，造模前7 d开始腹腔注射62.5，125，250 mg/kg氧化槐定碱或灌胃6 mg/kg尼莫地平，1次/d。再灌注后24 h取小鼠损伤脑组织进行检测。结果发现，125，250 mg/kg氧化槐定碱和尼莫地平均可降低模型小鼠的神经功能缺陷评分，减少模型小鼠脑梗死体积，降低模型小鼠损伤脑组织含水量，可见氧化槐定碱对脑缺血再灌注损伤具有保护作用。进一步探讨其相关机制发现，62.5，125，250mg/kg氧化槐定碱和尼莫地平均可增加模型小鼠损伤脑组织ATP含量，降低丙二醛和一氧化氮含量；提高损伤脑组织超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、乳酸脱氢酶活性，降低一氧化氮合成酶活性。同时，250 mg/kg氧化槐定碱和尼莫地平可明显抑制模型小鼠损伤脑皮质N-甲基-D-天冬氨酸受体1亚单位mRNA和蛋白表达。作者认为，氧化槐定碱对脑缺血再灌注损伤的保护作用与抗氧化应激、抑制N-甲基-D-天冬氨酸受体1亚单位表达有关。

关键词: 神经再生, 中医药, 脑损伤, 氧化槐定碱, 缺血再灌注损伤, 氧化应激, N-甲基-D-天冬氨酸受体, 神经保护, 基金资助文章

Abstract:

Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was established using middle cerebral artery occlusion in mice. Both 62.5, 125, and 250 mg/kg oxysophoridine, via intraperitoneal injection, and 6 mg/kg nimodipine, via intragastric administration, were administered daily for 7 days before modeling. After 24 hours of reperfusion, mice were tested for neurological deficit, cerebral infarct size was assessed and brain tissue was collected. Results showed that oxysophoridine at 125, 250 mg/kg and 6 mg/kg nimodipine could reduce neurological deficit scores, cerebral infarct size and brain water content in mice. These results provided evidence that oxysophoridine plays a protective role in cerebral ischemia/reperfusion injury. In addition, oxysophoridine at 62.5, 125, and 250 mg/kg and 6 mg/kg nimodipine increased adenosine-triphosphate content, and decreased malondialdehyde and nitric oxide content. These compounds enhanced the activities of glutathione-peroxidase, superoxide dismutase, catalase, and lactate dehydrogenase, and decreased the activity of nitric oxide synthase. Protein and mRNA expression levels of N-methyl-D-aspartate receptor subunit NR1 were markedly inhibited in the presence of 250 mg/kg oxysophoridine and 6 mg/kg nimodipine. Our experimental findings indicated that oxysophoridine has a neuroprotective effect against cerebral ischemia/reperfusion injury in mice, and that the effect may be due to its ability to inhibit oxidative stress and expression of the N-methyl-D-aspartate receptor subunit NR1.

Key words: neural regeneration, traditional Chinese medicine, brain injury, oxysophoridine, ischemia/reperfusion injury, oxidative stress, N-methyl-D-aspartate receptor, neuroprotection, grants-supported paper, neuroregeneration