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丹参葛根汤对大鼠心肌缺血/再灌注损伤的急性治疗作用通过氧化还原敏感的 PKCɛ/mK(ATP)通路。

Acute treatment with Danshen-Gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive PKCɛ/mK(ATP) pathway in rats.

机构信息

Section of Biochemistry and Cell Biology, Division of Life Science, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China.

出版信息

Phytomedicine. 2011 Aug 15;18(11):916-25. doi: 10.1016/j.phymed.2011.03.006. Epub 2011 Apr 29.

DOI:10.1016/j.phymed.2011.03.006
PMID:21855786
Abstract

Danshen-Gegen (DG) decoction, an herbal formulation comprising Radix Salvia Miltiorrhiza and Radix Puerariae Lobatae, is prescribed for the treatment of coronary heart disease in Chinese medicine. Experimental and clinical studies have demonstrated that DG decoction can reduce the extent of atherosclerosis. In the present study, using an ex vivo rat model of myocardial ischemia/reperfusion (I/R) injury, we investigated the myocardial preconditioning effect of an aqueous DG extract prepared from an optimized weight-to-weight ratio of Danshen and Gegen. Short-term treatment with DG extract at a daily dose of 1 g/kg and 2 g/kg for 3 days protected against myocardial I/R injury in rats. The cardioprotection afforded by DG pretreatment was paralleled by enhancements in mitochondrial antioxidant status and membrane structural integrity, as well as a decrease in the sensitivity of mitochondria to Ca²⁺-stimulated permeability transition in vitro, particularly under I/R conditions. Short-term treatment with the DG extract also enhanced the translocation of PKCɛ from the cytosol to mitochondria in rat myocardium, and this translocation was inhibited by α-tocopherol co-treatment with DG extract in rats. Short-term DG treatment may precondition the myocardium via a redox-sensitive PKCɛ/mK(ATP) pathway, with resultant inhibition of the mitochondrial permeability transition through the opening of mitochondrial K(ATP) channels. Our results suggest that clinical studies examining the effectiveness of DG extract given prophylactically in affording protection against myocardial I/R injury would be warranted.

摘要

丹参葛根(DG)汤是一种由丹参和葛根组成的草药配方,用于中医治疗冠心病。实验和临床研究表明,DG 汤可以减少动脉粥样硬化的程度。在本研究中,我们使用心肌缺血/再灌注(I/R)损伤的离体大鼠模型,研究了从丹参和葛根的优化重量比制备的 DG 水提取物的心肌预处理作用。每日 1 g/kg 和 2 g/kg 的 DG 提取物短期治疗 3 天可保护大鼠心肌免受 I/R 损伤。DG 预处理提供的心脏保护作用与线粒体抗氧化状态和膜结构完整性的增强以及线粒体对 Ca²⁺刺激的通透性转换的敏感性降低平行,特别是在 I/R 条件下。DG 提取物的短期治疗还增强了大鼠心肌中 PKCɛ 从细胞质向线粒体的易位,并且这种易位被 DG 提取物与α-生育酚共同处理抑制。DG 的短期治疗可能通过氧化还原敏感的 PKCɛ/mK(ATP)途径预处理心肌,通过打开线粒体 K(ATP)通道抑制线粒体通透性转换。我们的研究结果表明,进行临床研究检查预防性给予 DG 提取物对心肌 I/R 损伤的有效性是合理的。

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