Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia

Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia
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黄芪甲苷四甲基吡嗪对短暂性局灶性脑缺血所致脑缺血再灌注损伤的协同保护作用

DOI:
10.1016/j.jep.2011.12.023
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发表时间:
2012-03-06
影响因子:
5.4
通讯作者:
Wan, Haitong
Wan, Haitong
中科院分区:
医学2区
文献类型:
--
作者:
Yang, Jiehong;Li, Jinhui;Wan, Haitong

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民族药理学相关性:黄芪甲苷(ASG IV)和川芎嗪(TMPZ)作为治疗脑卒中和心肌缺血性疾病的糖苷类或生物碱类制剂的主要成分,已被广泛应用于心脑血管疾病的药物治疗中。将大鼠随机分为假手术组、缺血再灌注组和尼莫地平治疗组(ASG IV、ASG IV-TMPZ+尼莫地平)。采用F-18-氟-2-脱氧-D-葡萄糖进行微型正电子发射断层扫描(Micro-PET)评价治疗效果。结果:Micro-PET显像显示IR组右侧海马葡萄糖代谢明显低于Sham组(P <0.01),IR组右侧海马葡萄糖代谢明显低于Sham组(P < 0.01)。ASG IV和ASG IV-TMPZ治疗可逆转模型组糖代谢下降(分别为P < 0.05和P < 0.01)。IR组Caspase-3 mRNA水平、MDA含量和iNOS活性均较假手术组升高,SOD活性和Bcl-2表达较假手术组降低(P < 0.01)。ASG IV-TMPZ和ASG IV可逆转IR引起的Caspase-3 mRNA、MDA含量和iNOS活性的下调,以及SOD活性和Bcl-2表达的上调(P < 0.05)。结论:ASG IV-TMPZ对大鼠局灶性脑缺血再灌注损伤具有协同保护作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological relevance: Astragaloside IV and tetramethylpyrazine have been extensively used in the cardio-cerbrovascular diseases of medicine as a chief ingredient of glycoside or alkaloid formulations for the treatment of stroke and myocardial ischemia diseases.Aim of the study: To investigate the effects of astragaloside IV (ASG IV) and tetramethylpyrazine (TMPZ) on cerebral ischemia-reperfusion (IR) injury model in rat model.Materials and methods: Rats were randomly divided into the following five groups: sham group, IR group and treatment group including ASG IV, ASG IV-TMPZ and nimodipine treatment. The therapeutic effect was evaluated by micro-positron emission tomography (Micro-PET) using F-18-fluoro-2-deoxy-D-glucose. The neurological examination, infarct volume and the levels of oxidative stress- and cell apoptosis-related molecules were assessed.Results: Micro-PET imaging showed that glucose metabolism in the right hippocampus was significantly decreased in the IR group compared to the sham group (P < 0.01). ASG IV and ASG IV-TMPZ treatments reversed the decreased glucose metabolism in the model group (P < 0.05 and P < 0.01, respectively). IR induced the increase of Caspase-3 mRNA levels, MDA content and iNOS activity, but it caused the decrease of SOD activity and Bcl-2 expression compared the sham group (P < 0.01). ASG IV-TMPZ and ASG IV reversed the IR-induced changes of these parameters, i.e. the down regulation of Caspase-3 mRNA, MDA content and iNOS activity, and the up regulation of SOD activity and Bcl-2 expression (P < 0.05).Conclusion: This study showed that ASG IV-TMPZ played a pivotal synergistic protective role against focal cerebral ischemic reperfusion damage in a rat experimental model. (C) 2011 Elsevier Ireland Ltd. All rights reserved.