芍药苷诱导药理预适应抗脑缺血的神经保护作用

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (5): 504-511.

芍药苷诱导药理预适应抗脑缺血的神经保护作用

王国峰¹, 陈冬梅²

¹济南军区总医院老年病五科,济南 250031,山东;
²中国科学院上海药物研究所,上海 201203

收稿日期:2006-04-17 修回日期:2006-06-14 发布日期:2020-10-29
作者简介:王国峰,男,在读硕士,主治医师,研究方向为老年心脑血管疾病的治疗及机制研究。 E-mail:gfw3123@163.com。陈冬梅,女,博士,研究方向为神经药理学和分子药理学

Neuroprotective effects of paeoniflorin against cerebral ischemia through pharmacological preconditioning

WANG Guo-feng¹, CHEN Dong-mei²

¹The General Hospital of Jinan Military Area Command of PLA, Jinan 250031, Shandong, China;
²Shanghai Drug Institute, Chinese Academy of Medical Sciences, Shanghai 201203, China

Received:2006-04-17 Revised:2006-06-14 Published:2020-10-29

摘要/Abstract

摘要： 目的: 研究传统中药处方芍药甘草汤中的化合物芍药苷(paeoniflorin,PF)对大鼠大脑中动脉梗塞(MCAO)的神经保护作用,为脑卒中的防治提供新思路。方法: 脑缺血90 min,再灌24 h,观察PF 预适应对梗塞体积及神经症状的影响;采用RT-PCR 和Western blot 研究PF 对环氧酶-2(cyclooxygenase-2,COX-2)和5-脂氧酶(5-lipoxygenase,5-LOX)基因、蛋白表达及MAPK 通路的影响。结果: PF(20、40mg/kg,i.p.)在MCAO 前48 h 给药,可剂量依赖性地降低梗塞体积、改善神经功能;PF(20mg/kg,i.p.)于MCAO前24、48h和5d预给药,可时间依赖性地诱导神经保护作用,PF(20mg/kg,i.p.,48 h)预给药可显著降低脑缺血再灌中COX-2 mRNA和蛋白及5-LOX 蛋白的过表达,抑制MAPK 通路的激活。结论: PF通过药理预适应产生神经保护作用,其机制为抑制COX-2和5-LOX的基因或蛋白表达并抑制MAPK 通路的激活。

关键词: 大脑中动脉梗塞, 药理预适应, 花生四烯酸代谢, 环氧酶-2, 5-脂氧酶

Abstract: AIM: To investigate the neuroprotective effects of paeoniflorin (PF) , the principal component of Paeoniae Radix prescribed in traditional Chinese medicine against the damage of rat middle cerebral artery occlusion (MCAO) and reperfusion through pharmacological preconditioning (PPC) and its molecular mechanisms, in order to offer novel drug targets and therapeutic strategies against ischemic stroke. METHODS: In rat MCAO and reperfusion model, the effects of PF pretreatment through PPC on the infarct volume and neurological deficits were examined. Furthermore, the mRNA or protein expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) have been examined after PF preconditioning using RT-PCR and Western Blot analyses. Finally, the protein expressions of MAPK signaling effectors were examined after PF preconditioning. RESULTS: At a dosage of 20 or 40 mg kg, PF preconditioning reduced the infarct volume dose-dependently and reversed the neurological deficits caused by ischemia. Similarly, the ameliorative effects on infarct size and neurological impairment induced by MCAO emerged as well at a time-dependent manner when PF was administered 24, 48 h or 5 d before MCAO at the dose of 20 mg kg. The over expressions ofCOX-2 mRNA and protein and 5-LOX protein in ischemia were reversed by PF preconditioning. The activation of MAPK signaling pathway was also inhibited by PF preconditioning. CONCLUSION: The PPC could be induced by PF, mimicking the effects of ischemic preconditioning. The molecular mechanisms underlying its ameliorative effects are through inhibiting the inflammation involved in arachidonic acid metabolism and the activation of MAPK signaling pathway.

Key words: middle cerebral artery occlusion, pharmacological preconditioning, arachidonic acid metabolism, cyclooxygenase-2, 5-lipoxygenase

中图分类号:

R965.2
R966

王国峰, 陈冬梅. 芍药苷诱导药理预适应抗脑缺血的神经保护作用[J]. 中国临床药理学与治疗学, 2007, 12(5): 504-511.

WANG Guo-feng, CHEN Dong-mei. Neuroprotective effects of paeoniflorin against cerebral ischemia through pharmacological preconditioning[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(5): 504-511.

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