吴茱萸次碱对血管收缩及RhoA/MLCP-MLC信号通路的影响

摘要

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.%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.