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

吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响(英文)

作　　者：王秀坤[1,2] 王玉刚[1] 柴玉爽[1] 胡珺[1] 詹宏磊[1] 邢东明[1] 游雪甫[2] 王智民[3] 杨秀伟[4] 雷帆[1] 杜力军[1] 

机构地区：[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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2012年第5期436-447,共12页中国药学（英文版）

基　　金：National Natural Science Foundation of China (Grant No.30801523,30973896,and 81073092);the Projects of Science Research for the 11th 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);the National S&T Major Special Project for New Drug R&D of China (Grant No.2012ZX09102-201-008,2012ZX09103-201-041and2011ZX09101-002-11)

摘　　要：The aims of the present study are to investigate the effect of vasoconstriction and to explore the mechanism of rutae- carpine. 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 （IP 3 R） 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 Ca 2＋ and enhanced the IP 3 R expression, which connects with 1,4,5-triphosphate to evoke the release of Ca 2＋ 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.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(300μg/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：RUTAECARPINE Blood vessel Myosin light chain 

分 类 号：R285[医药卫生—中药学]