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吴茱萸次碱通过抑制TLR4/NF-κB信号通路保护大鼠心肌缺血/再灌注损伤

杨晶 张晓坚 胡长平

中国药理学通报2017,Vol.33Issue(12):1707-1712,6.
中国药理学通报2017,Vol.33Issue(12):1707-1712,6.DOI:10.3969/j.issn.1001-1978.2017.12.016

吴茱萸次碱通过抑制TLR4/NF-κB信号通路保护大鼠心肌缺血/再灌注损伤

Rutaecarpine protects against myocardial ischemia / reperfusion injury through inhibiting Toll-like receptor 4 / NF-κB signaling pathway in rats

杨晶 1张晓坚 1胡长平2

作者信息

  • 1. 郑州大学第一附属医院药学部,河南 郑州 450052
  • 2. 中南大学湘雅药学院药理学系,湖南 长沙 410078
  • 折叠

摘要

Abstract

Aim To investigate whether the protection of rutaecarpine against myocardial ischemia / reperfusion (I/ R ) injury is mediated by Toll-like receptor 4 (TLR4)/ NF-κB pathway,and whether these effects are related to the release of calcitonin gene-related peptide(CGRP)in plasma. Methods Sprague-Daw-ley rats were subjected to 60 min of ligation of the left anterior descending coronary followed by 3h of reperfu-sion to induce I/ R injury. Rats were pretreated with rutaecarpine 10 min before the ligation,and some rats were pretreated with capsazepine 2 min before rutae-carpine administration. Myocardial infarct size,CGRP concentration in plasma and creatine kinase (CK)ac-tivity in serum were measured. The expression of TLR4 mRNA in myocardial tissue was determined by RT-PCR. The protein expression of TLR4 and NF-κB in myocardial tissue was analyzed by immunohistochemis-try. Results Rutaecarpine (100,300 μg · kg - 1 , iv)significantly reduced the infarct size and the serum CK activity concomitantly with the increase in plasma CGRP concentration (P < 0. 05). Importantly,the ex-pression of TLR4 (both mRNA and protein)and NF-κB (protein)was increased by myocardial I/ R injury, and dramatically inhibited by rutaecarpine pretreatment (P < 0. 05). All these effects of rutaecarpine were a-bolished by capsazepine (1. 5 mg·kg - 1 ,iv),a spe-cific antagonist for vanilloid receptor-1. Conclusion Rutaecarpine protects against myocardial I/ R injury by inhibiting TLR4 / NF-κB pathway,which is related to the increased release of CGRP.

关键词

Toll样受体4/降钙素基因相关肽/缺血/再灌注损伤/吴茱萸次碱/心脏/大鼠

Key words

Toll-like receptor 4/calcitonin gene-re-lated peptide/ischemia / reperfusion injury/rutae-carpine/heart/rats

分类

医药卫生

引用本文复制引用

杨晶,张晓坚,胡长平..吴茱萸次碱通过抑制TLR4/NF-κB信号通路保护大鼠心肌缺血/再灌注损伤[J].中国药理学通报,2017,33(12):1707-1712,6.

基金项目

河南省医学科技攻关计划省部共建项目 (No 201601001) (No 201601001)

河南省医学科技攻关计划项目 (No 201403019) (No 201403019)

中国药理学通报

OA北大核心CSCDCSTPCD

1001-1978

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