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丹参酮 VI 衍生物对灌注大鼠心脏缺氧后收缩功能障碍的影响。

Effects of tanshinone VI derivatives on post-hypoxic contractile dysfunction of perfused rat hearts.

作者信息

Yagi A, Okamura N, Tanonaka K, Takeo S

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.

出版信息

Planta Med. 1994 Oct;60(5):405-9. doi: 10.1055/s-2006-959519.

DOI:10.1055/s-2006-959519
PMID:7997465
Abstract

The present study was undertaken to elucidate the effects of sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen succinate (2), and disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue sodium, potassium, calcium, and magnesium contents after reoxygenation, and release of creatine kinase and purines and bases (ATP metabolites) during hypoxia/reoxygenation were also examined. The derivatives were dissolved in a Krebs-Henseleit buffer and administered at concentrations of 42 nM into the buffer. Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of creatine kinase and ATP metabolites, suggesting hypoxia/reoxygenation-induced functional and morphological damage. The tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of creatine kinase and ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of tanshinone VI. The results suggest that water-soluble tanshinone VI derivatives, like tanshinone VI itself, are beneficial for hypoxia/reoxygenation injury.

摘要

本研究旨在阐明丹参酮Ⅵ的水溶性衍生物丹参酮Ⅵ 1 -酚盐(1)、1'-O-氢琥珀酰丹参酮Ⅵ 1-O-氢琥珀酸盐(2)和1'-O-琥珀酰丹参酮Ⅵ 1-O-琥珀酸二钠(3)对离体灌注大鼠心脏缺氧后收缩恢复的影响。将这些影响与之前测试的丹参酮Ⅵ的影响进行比较。心脏在缺氧条件下灌注20分钟,然后再给氧45分钟,并测定其心脏功能。还检测了再给氧后组织中钠、钾、钙和镁含量的变化,以及缺氧/再给氧期间肌酸激酶、嘌呤和碱基(ATP代谢产物)的释放。将衍生物溶解在Krebs-Henseleit缓冲液中,并以42 nM的浓度加入缓冲液中。缺氧/再给氧导致心脏收缩力略有恢复、组织离子浓度显著改变以及肌酸激酶和ATP代谢产物大量释放,提示缺氧/再给氧诱导了功能和形态学损伤。丹参酮Ⅵ衍生物改善了缺氧后的收缩恢复,这与组织离子浓度的恢复以及缺氧/再给氧心脏中肌酸激酶和ATP代谢产物释放的减少有关。这些化合物的疗效与丹参酮Ⅵ相似。结果表明,水溶性丹参酮Ⅵ衍生物与丹参酮Ⅵ本身一样,对缺氧/再给氧损伤有益。

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