吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响

doi:10.5246/jcps.2012.05.058

吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响

王秀坤, 王玉刚, 柴玉爽, 胡珺, 詹宏磊, 邢东明, 游雪甫, 王智民, 杨秀伟, 雷帆, 杜力军^*

1. 清华大学教育部蛋白质科学重点实验室, 生命科学学院医学院药物药理研究室, 北京 100084
2. 中国医学科学院北京协和医学院医药生物技术研究所, 北京 100050
3. 中国中医科学院中药研究所, 北京 100700
4. 北京大学医学部药学院, 北京 100191

收稿日期:2011-11-20 修回日期:2012-05-20 出版日期:2012-09-15 发布日期:2012-09-15
通讯作者: 杜力军*

Comprehensive study of rutaecarpine on vascular constriction relative to RhoA/MLCP-MLC signaling

Xiukun Wang, Yugang Wang, Yushuang Chai, Jun Hu, Honglei Zhan, Dongming Xing, Xuefu You, Zhimin Wang, Xiuwei Yang, Fan Lei, Lijun Du^*

1. Protein Science Laboratory of the Ministry of Education, Laboratory of Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
2. Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
4. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-11-20 Revised:2012-05-20 Online:2012-09-15 Published:2012-09-15
Contact: Lijun Du*

摘要/Abstract

摘要： 本文对吴茱萸次碱的收缩血管效应及其机制进行了研究。结果表明, 吴茱萸次碱体外可明显的引起大鼠胸主动脉血管平滑肌收缩。与血管平滑肌收缩相关的信号蛋白Rho激酶 (RhoA)和IP₃受体 (IP₃R)的抑制剂可以抑制吴茱萸次碱的缩血管效应。血管平滑肌细胞A7r5的实验发现, 吴茱萸次碱 (300 μg/L)可以明显升高胞内Ca²⁺浓度, 促进IP₃R的mRNA表达, 而后者与胞内Ca²⁺浓度升高有关。预先使用RhoA抑制剂H-1152, 吴茱萸次碱仍能使RhoA mRNA表达升高。此外, 吴茱萸次碱能够促进肌球蛋白轻链磷酸酶 (MLCP)以及肌球蛋白轻链 (MLC)的磷酸化。提示吴茱萸次碱的缩血管效应与RhoA/MLCP-MLC信号转导通路有关。本工作对于深入认识吴茱萸次碱的药理活性具有重要的意义。

关键词: 吴茱萸次碱, 血管, 肌球蛋白轻链

Abstract: The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutaecarpine. The research findings showed that rutaecarpine could induce contractions of the rat thoracic aorta in vitro. The inhibitors of Rho-kinase and inositol 1,4,5-triphosphate receptor (IP₃R) could suppress the effect of rutaecarpine-induced vasoconstriction. In the study of A7r5 cells (a line of smooth muscle cells), 300 μg/L rutaecarpine promoted the concentration of intracellular Ca²⁺and enhanced the IP₃R expression, which connects with 1,4,5-triphosphate to evoke the release of Ca²⁺from the intracellular stores. Rutaecarpine increased the RhoA mRNA expression when the cells were pretreated with inhibitor H-1152, and improved the levels of phosphorylation of myosin light chain phosphatase (MLCP) and myosin light chain (MLC). These results suggest that rutaecarpine plays a role in vasoconstriction relative to the RhoA/MLCP-MLC signaling pathway, which denotes a new field of rutaecarpine in pharmacology.

Key words: Rutaecarpine, Blood vessel, Myosin light chain

中图分类号:

R962.1

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 30801523, 30973896, and 81073092), the Projects of Science Research for the 11^th Five-Year Plan of the Ministry of Science and Technology of China (Grant No. 2006BAI08B03-09), the China's Post-Doctoral Science Fund (Grant No.20080440418), and the National S&T Major Special Project for New Drug R&D of China (Grant No. 2012ZX09102-201-008, 2012ZX09103-201-041 and 2011ZX09101-002-11).
^*Corresponding author. Tel.: 86-10-62773630

王秀坤, 王玉刚, 柴玉爽, 胡珺, 詹宏磊, 邢东明, 游雪甫, 王智民, 杨秀伟, 雷帆, 杜力军^*. 吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响[J]. , DOI: 10.5246/jcps.2012.05.058.

Xiukun Wang, Yugang Wang, Yushuang Chai, Jun Hu, Honglei Zhan, Dongming Xing, Xuefu You, Zhimin Wang, Xiuwei Yang, Fan Lei, Lijun Du^* . Comprehensive study of rutaecarpine on vascular constriction relative to RhoA/MLCP-MLC signaling[J]. , DOI: 10.5246/jcps.2012.05.058.

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