丹参酮IIA衍生物对大鼠心肌缺血再灌注损伤的保护作用

doi:10.5246/jcps.2018.01.001

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (1): 1-13.DOI: 10.5246/jcps.2018.01.001

• 【研究论文】 • 下一篇

丹参酮IIA衍生物对大鼠心肌缺血再灌注损伤的保护作用

沈婉丽^1,2,3#, 于飞^4#, 徐璐^2,3, 陈聪^2,3, 曹旖旎^2,3, 刘姝^1,2,3, 韩南银⁴, 王超⁴, 祁荣^1,2,3*

1. 石河子大学药学院, 新疆石河子 832000
2. 北京大学医学部北京大学心血管研究所, 北京 100191
3. 北京大学医学部分子药剂学与新药递送系统北京市重点实验室, 北京 100191
4. 北京大学医学部药学院, 北京 100191

收稿日期:2017-10-09 修回日期:2017-12-11 出版日期:2018-02-28 发布日期:2018-01-03
通讯作者: Tel./Fax: +86-010-82805164, E-mail: ronaqi@bjmu.edu.cn
基金资助:
The National Natural Science Foundation of China (Grant No. 81360054).

Protective effects of tanshinone IIA derivative on myocardial ischemia/reperfusion injury in rats

Wanli Shen^1,2,3#, Fei Yu^4#, Lu Xu^2,3, Cong Chen^2,3, Yini Cao^2,3, Shu Liu^1,2,3, Nanyin Han⁴, Chao Wang⁴, Rong Qi^1,2,3*

1. School of Pharmacy, Shihezi University, Shihezi 832000, China
2. Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing 100191, China
3. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing 100191, China
4. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2017-10-09 Revised:2017-12-11 Online:2018-02-28 Published:2018-01-03
Contact: Tel./Fax: +86-010-82805164, E-mail: ronaqi@bjmu.edu.cn
Supported by:
The National Natural Science Foundation of China (Grant No. 81360054).

摘要/Abstract

摘要：

丹参酮IIA是中药丹参中的主要活性成分, 研究表明丹参酮IIA对缺血再灌注损伤具有保护作用。但丹参酮IIA的水溶性较差, 限制了其临床应用。本研究以丹参酮IIA为对照, 在大鼠缺血再灌注损伤模型上, 评价丹参酮IIA与N-甲基-D-葡萄糖胺反应得到的一种新的水溶性的丹参酮IIA衍生物对心肌缺血再灌注损伤的保护作用与机制。结果表明, 采用丹参酮IIA衍生物预处理能显著减少大鼠心肌缺血再灌注损伤引起的心肌炎症浸润及氧化损伤, 减少乳酸脱氢酶(LDH)及丙二醛(MDA)的活性; 降低核转录因子κB(NF-κB)的基因表达量; 上调血红素氧合酶(HO-1)的基因表达; 但对超氧化物歧化酶(T-SOD)的含量及SOD-1基因的表达量无显著调节作用。本研究结论表明丹参酮IIA衍生物具有保护心肌缺血再灌注损伤的作用, 机制与其显著抑制炎症与氧化损伤有关。

关键词: 心肌缺血再灌注损伤, 丹参酮IIA衍生物, 丹参酮IIA

Abstract:

Tanshinone IIA (TSIIA) is the major bioactive constituent of Salvia miltiorrhiza Bunge, a Chinese herbal medicine, which has protective effects on myocardial ischemia/reperfusion (MIR) injury. However, the cardioprotective effects of TSIIA as well as its clinical use were limited due to its poor water solubility. The objective of this study was to evaluate whether Tanshinone IIA derivative (TD), a new water soluble compound synthesized by TSIIA and N-Methyl-D-Glucamine, had protective effects on MIR injury and what the related mechanism was. The cardioprotective effects of TD were evaluated and compared with TSIIA in a rat MIR model. The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase (LDH) and malondialdehyde (MDA), decreasing expression of nuclear factor-κ-gene binding (NF-κB) and upregulating expression of heme oxygenase (HO-1), but having no effect on the content of total superoxide dismutase (T-SOD) and mRNA expression of superoxide dismutase (SOD-1). Thus, our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.

Key words: Myocardial ischemia/reperfusion, Tanshinone IIA derivative, Tanshinone IIA

中图分类号:

R962

Supporting:

沈婉丽, 于飞, 徐璐, 陈聪, 曹旖旎, 刘姝, 韩南银, 王超, 祁荣. 丹参酮IIA衍生物对大鼠心肌缺血再灌注损伤的保护作用[J]. 中国药学(英文版), 2018, 27(1): 1-13.

Wanli Shen, Fei Yu, Lu Xu, Cong Chen, Yini Cao, Shu Liu, Nanyin Han, Chao Wang, Rong Qi. Protective effects of tanshinone IIA derivative on myocardial ischemia/reperfusion injury in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(1): 1-13.

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丹参酮IIA衍生物对大鼠心肌缺血再灌注损伤的保护作用

Protective effects of tanshinone IIA derivative on myocardial ischemia/reperfusion injury in rats

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