杜仲不同炮制品舒张血管作用比较及作用机制研究

Comparative study of the vasodilatation effect of different processed products of Eucommiae Cortex in vitro and mechanisms involved in vasodilatation

目的:观察杜仲3种炮制品(盐炙烘制品、盐炙炒制品和生品)的木脂素类对大鼠肠系膜上动脉血管环的舒张作用,并探讨其相关机制。方法:使用Myograph动态描记系统,观察3种炮制品木脂素类对氯化钾溶液(60m M)、苯肾上腺素(PE)预收缩血管环的舒张作用;并分别用内皮途径抑制剂(鸟苷酸环化酶抑制剂[ODQ(10μM)]、一氧化氮合酶可逆抑制剂[L-NAME(100μM)]、环氧合酶抑制剂[Indo(5μM)])以及钾离子通道抑制剂(KV阻断剂4-AP、KCa阻断剂TEA、Kir阻断剂BaCl_2、KATP阻断剂Glib)处理血管,探讨杜仲木脂素(EUL)舒血管作用机制。结果:在杜仲的3种炮制品中,盐炙烘制品中提取的木脂素类舒血管作用最强,且对氯化钾溶液(60m M)和PE(10-5M)预收缩的血管都有浓度依赖性的舒张作用。另外,在内皮途径抑制剂中,L-NAME对杜仲木脂素类化合物(10-3g/ml)引起的舒张作用有显著的抑制作用,而ODQ和Indo则无影响;在钾离子通道抑制剂中,BaCl_2对杜仲木脂素类化合物(10-3g/ml)引起的舒张作用有显著的抑制作用,4-AP、Gli和TEA则无影响。结论:杜仲盐炙烘制品对大鼠肠系膜上动脉血管环舒张作用最强,其作用机制为杜仲木脂素通过内皮依赖途径(促进NO释放)和非内皮依赖途径(激活内向整流K+通道)促进肠系膜上动脉的舒张。

Objective： To investigate the vasorelaxant effect of extractives of three processed Eucommiae Cortex（EUL）（Baking and Stir products with salt,Crude products） on rat superior mesenteric arterial rings as well as its mechanisms. Methods： Isometric tensions of rat superior mesenteric arterial rings were recorded by a sensitive myograph system in vitro. We measured isometric tension changes of potassium chloride（KCl,60 m M）,or phenylephrine（PE,10^-5 M） preconstricted rat superior mesenteric artery rings after the treatment of three processed Eucommiae Cortex at different concentrations,respectively. We also observed the vasorelaxant effect of Eucommiae Cortex on KCl（60 m M）-preconstricting rat superior mesenteric arterial rings after incubating with inhibitors of Endothelial mechanism,the endothelial NO synthase（e NOS） inhibitor L-NAME,the guanylate cyclase inhibitor ODQ and the cyclooxygenase inhibitor Indo,and inhibitors of Potassium ion channel,4-AP（KV channels blockers）,and TEA（KCa channels blockers）,and Ba Cl2（Kir channels blockers）,and Glib（KATP channels blockers）,respectively. The mechanism involved in vasodilatation induced by EUL was researched. Resnlts： The vasorelaxant effect of baking products with salt was best in three processed products. EUL（10^-3 g/ml） relaxed the superior mesenteric artery rings concentration-dependently by pre-contracted by KCl（60 m M） and PE. In inhibitors of Endothelial mechanism,the vasodilatation treated by EUL in KCl（60 m M）-preconstricted rat mesenteric artery,L-NAME had the obvious inhibitory action（P〈0. 05）,but ODQ and Indo had no effect. In inhibitors of Potassium channel,the vasodilatation treated by EUL（10^-3 g/ml） in KCl（60 m M）-preconstricted rat mesenteric artery,Ba Cl2 had the obvious inhibitory action,but 4-AP,Gli,TEA had no effect. Conclusion： EUL（10^-3 g/ml） of baking products with salt could relax precontracted rat superior mesenteric arterial rings by KCl（60 m M）,and its vasodilatation is strong. Its mechanisms are that EUL induces the relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway（promoting NO release）,and also through an endothelium-independent pathway（activating inward rectifying potassium channel blocker）.