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补阳还五汤对大鼠局灶性脑缺血/再灌注损伤的神经保护作用-时间窗和机制。

Neuroprotective effect of Buyang Huanwu decoction against focal cerebral ischemia/reperfusion injury in rats--time window and mechanism.

机构信息

Department of Neurology, The Xuzhou Medical College Affiliated Huai'an Hospital, Huai'an, Jiangsu, China.

出版信息

J Ethnopharmacol. 2012 Mar 27;140(2):339-44. doi: 10.1016/j.jep.2012.01.026. Epub 2012 Jan 25.

DOI:10.1016/j.jep.2012.01.026
PMID:22306289
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Buyang Huanwu Decoction, a traditional Chinese medicine, consists of different herbal medicines, and has been traditionally used for centuries to treat paralysis and stroke. However, its optimal therapeutic time window and the mechanism are still unclear.

AIM OF THE STUDY

This study was designed to explore the therapeutic time window and mechanism of Buyang Huanwu Decoction on transient focal cerebral ischemia/reperfusion injury.

MATERIALS AND METHODS

Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats, and 40g/kg of Buyang Huanwu Decoction was intragastrically infused at different time points, and the same dose was infused every 24h for 3 days. The level of glutamate in cerebrospinal fluid and the expression of metabotropic glutamate receptor-1 RNA in striatum were detected before, during, and after ischemia/reperfusion. Neurological deficit scores and brain infarction volumes were measured at 72h after reperfusion.

RESULT

Cerebral ischemia/reperfusion resulted in significant neurological deficit and extensive cerebral infarct volume, associated with a large amount of glutamate in cerebrospinal fluid and elevation of metabotropic glutamate receptor-1 RNA expression. Buyang Huanwu Decoction significantly suppressed the release of glutamate, and reduced the expression of metabotropic glutamate receptor-1 RNA. The neurological defect score and infarction volume were significantly improved by administration of Buyang Huanwu Decoction, when compared with the Ischemia group.

CONCLUSIONS

Administration of Buyang Huanwu Decoction, within 4h of post-transient focal stroke, reduced significant cerebral ischemia/reperfusion damage. The neuroprotective mechanism of Buyang Huanwu Decoction is, in part, associated with the down-regulation of metabotropic glutamate receptor-1 RNA and inhibition of glutamate release resulting from cerebral ischemia.

摘要

民族药理学相关性

补阳还五汤是一种中药方剂,由多种草药组成,传统上用于治疗瘫痪和中风已有数百年的历史。然而,其最佳治疗时间窗和机制仍不清楚。

研究目的

本研究旨在探讨补阳还五汤对短暂性局灶性脑缺血/再灌注损伤的治疗时间窗和机制。

材料和方法

采用雄性 Sprague-Dawley 大鼠大脑中动脉闭塞模型,在不同时间点给予 40g/kg 的补阳还五汤灌胃,每天 24 小时给予相同剂量,连续 3 天。在缺血/再灌注前、中、后检测脑脊液中谷氨酸水平和纹状体中代谢型谷氨酸受体-1 RNA 的表达。在再灌注后 72 小时测量神经功能缺损评分和脑梗死体积。

结果

脑缺血/再灌注导致明显的神经功能缺损和广泛的脑梗死体积,伴随着大量的脑脊液谷氨酸释放和代谢型谷氨酸受体-1 RNA 表达升高。补阳还五汤能显著抑制谷氨酸的释放,降低代谢型谷氨酸受体-1 RNA 的表达。与缺血组相比,补阳还五汤给药后神经功能缺损评分和梗死体积显著改善。

结论

在短暂性局灶性中风后 4 小时内给予补阳还五汤,可减轻明显的脑缺血/再灌注损伤。补阳还五汤的神经保护机制部分与下调代谢型谷氨酸受体-1 RNA 以及抑制脑缺血引起的谷氨酸释放有关。

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