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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。
Objective: To study the vasoconstrictor effect of Evodia rutaecarpa and its mechanism. Methods: Evodia rutaecarpa extract was treated with dialysis bag (100D) and the in vitro and in vivo experiments were performed on Evodia rutaecarpa (ED,> 100D). Results: ED significantly increased cerebral blood flow in mice and induced the contraction of the thoracic aortic rings in rats, all of which had dose effects. ED on the basis of phenylephrine constriction can cause further contractile responses. The vasoconstriction activity of 250 mg · L-1 ED induced vasoconstriction was 113% of maximal contraction of 50 mmol·L-1 KCl, 78% of 10 μmol·L-1 phenylephrine and 20 mmol·L-1 of coffee Due to 183%. Phentolamine, an antagonist of cell surface alpha receptors, significantly inhibited vasoconstrictive activity of Evodia, whereas neither beta, M nor angiotensin II receptor antagonists propranolol, atropine, and losartan had any effect on ED contraction Vascular activity impact. Removal of extracellular calcium or use of L-type calcium channel antagonist nicardipine can significantly inhibit the vasoconstriction of ED, while calcium channel opener BAY-K8644 and potassium channel opener pinacidil ED Systolic blood vessels also have a certain effect. Studies of the possible signaling pathways by using selective receptor inhibitors on ED suggest that the use of myosin kinase (MLCK) inhibitors, RhoA inhibitors and inositol triphosphate (IP3) receptor inhibitors can inhibit ED activity, whereas Protein kinase C (PKC) inhibitors and extracellular signal-regulated kinase (ERK) inhibitors had no effect on Evodia activity. Conclusion: ED can induce calcium-dependent and calcium-independent vasoconstriction. The mechanisms include extracellular calcium influx, α-receptor, ROK and IP3 receptor signaling and MLCK activation. The evoked vasoconstriction of Evodia not only includes the regulatory mechanisms of the cellular membrane calcium channels but also the intracellular calcium regulation.