吴茱萸收缩血管作用的体内体外研究(英文)  

Comprehensive Study of Evodia rutaecarpa-induced Contraction on Blood Vascular in Vivo and in Vitro

作　　者：王秀坤[1,2] 王玉刚[1] 詹宏磊[1] 柴玉爽[1] 胡珺[1] 邢东明[1] 游学甫[2] 雷帆[1] 杜力军[1] 

机构地区：[1]清华大学生命科学学院医学院药物药理研究室,北京100084 [2]中国医学科学院中国协和医科大学医药生物技术研究所药理室,北京100050

出　　处：《中国天然药物》2011年第1期65-73,共9页

基　　金：国家十一五科技支撑计划项目(Nos. 90713043,30801523,30973896);中国博士后科学基金(No.20080440418);国家十一五"重大新药创制"科技重大专项(Nos. 2009ZX09103-301,2009ZX09502)~~

摘　　要：目的:对吴茱萸的收缩血管作用及其机制进行了研究。方法:吴茱萸提取物经透析袋(100D)处理后,对吴茱萸透析液(ED,>100D)进行了体内和体外实验研究。结果:ED能够明显增加小鼠脑血流,并能够诱导大鼠胸主动脉环的收缩,且均具有一定的剂量效应。在苯肾上腺素收缩血管的基础上ED能够引起进一步的收缩反应。250mg·L-1 ED的血管收缩活性,其诱导血管收缩的程度是50mmol·L-1 KCl最大收缩的113%,是10μmol·L-1苯肾上腺素的78%,为20mmol·L-1咖啡因的183%。细胞表面α受体的拮抗剂酚妥拉明,能够明显抑制吴茱萸收缩血管活性,而β,M和血管紧张素Ⅱ受体拮抗剂普萘洛尔、阿托品和氯沙坦均未对ED的收缩血管活性带来影响。去除细胞外的钙离子或者使用L-型钙离子通道拮抗剂尼卡地平可以显著地抑制ED的缩血管作用,而钙离子通道开放剂BAY-K8644和钾离子通道开放剂吡那地尔对ED收缩血管作用也有一定影响。利用选择性受体抑制剂对ED可能的信号通路研究显示,使用肌球蛋白激酶(MLCK)抑制剂、RhoA抑制剂和三磷酸肌醇(IP3)受体抑制剂均可以抑制ED的活性,而蛋白激酶C(PKC)抑制剂和胞外信号调节激酶(ERK)抑制剂对吴茱萸的活性则无影响。结论:ED能够引发钙依赖性和非钙依赖性血管收缩,其中机制包括细胞外钙内流,α受体、ROK和IP3受体信号通路以及MLCK的激活等。吴茱萸的收缩血管作用不仅包括细胞膜钙通道的调节机制也包括对细胞内钙的调节。AIM：Evodiae Fructus （fruit of Evodia rutaecarpa）,a blood vessel activator,has been used,with headache,migraine,shock etc.,for a long history in Chinese medical practice.However,previous studies supported the vessel relaxation and the potential action on cardiac and cerebral blood circulation of vessel contraction.The present study was designed to explore it effects on contraction and the relative mechanism.METHODS：Evodiae Fructus was extracted by dialysis tubing （in diameter of 100 Dalton cutoff） and the effect of the evodia dialyzed （ED） （ 100 D） was studied in vivo and in vitro.RESULTS：ED could dose-dependently promote the micro-cerebral blood flow in mice and induced the contraction of rat thoracic aorta at rest and phenylephrine pre-evoked state.Compared with the vasocontraction under 50 mmol·L-1 KCl,250 mg·L-1 ED increased by 113%.The effect was inhibited by α-adrenergic receptor blocker phentolamine,instead of β-adrenergic receptor blocker propranolol,M-adrenaline receptor blocker atropine,and angiotensin II receptor blocker losartan.The depletion of extracellular calcium decreased the contraction induced by ED and the addition of L-type calcium ion channel antagonist （nicardipine）,calcium ion channel activator （BAY-K8644） and potassium ion channel opener （pinacidil） significantly affected the contraction induced by ED.Selected inhibitors were used to investigate the possible mechanism of ED-induced vasocontraction.Inhibitors of myosin light chain kinase （MLCK）,Rho-kinase （ROK） and inositol 1,4,5-triphosphate （IP3） receptor suppressed the effect of ED.CONCLUSION：ED induced Ca2＋-dependent and Ca2＋-independent contraction,the Ca2＋ influx,α-adrenoceptor,ROK and IP3 receptor signal pathways and MLCK activation might be involved in the contractile process.These results suggested that Evodiae Fructus could increase the blood vessel contraction by the effect on calcium channel on the membrane.

关 键 词：吴茱萸 透析 血管收缩 

分 类 号：R965[医药卫生—药理学]