益母草碱对大鼠肠系膜动脉的力学效应及其机制探讨

The mechanical effect and mechanism of leonurine on rat mesenteric artery

目的探讨益母草碱对大鼠肠系膜动脉的力学效应及其机制。方法 50只SD大鼠随机分为对照组,益母草碱低、中、高剂量组,每组10只,另外10只做离体实验。益母草碱组给予益母草碱生理盐水悬浊液,对照组给予等量生理盐水分别灌胃。4周后测定各组大鼠血清中NO和血浆中ET-1含量,分离肠系膜三级动脉HE染色。用微血管测定系统观察益母草碱对内皮完整和去内皮的离体实验组肠系膜三级动脉环舒张效应,以及一氧化氮合酶抑制剂(L-NAME)、可溶性鸟苷酸环化酶(s GC)抑制剂(NS-2028)和钙离子通道拮抗剂硝苯地平孵育后益母草碱对动脉环的舒张效应。结果益母草碱灌胃组大鼠血清中NO和血浆中ET-1含量较对照组低,并且具有浓度依赖效应,ET-1较NO降低的更快;HE染色显示益母草碱组血管壁较对照组薄,并且具有浓度依赖效应。益母草碱对内皮完整的动脉环有直接舒张作用,对去内皮和L-NAME、NS-2028、硝苯地平孵育之后的动脉环舒张效应均明显减弱。结论益母草碱灌胃对大鼠肠系膜动脉具有保护作用,益母草碱对离体大鼠肠系膜动脉环具有浓度依赖性和内皮依赖性的舒张效应,这种舒张效应可能与NO-s GC-c GMP信号通路及L型钙离子通道有关。

Objective To investigate the mechanical effect and mechanism of leonurine on rat mesenteric artery. Methods 50 healthy male Sprague-Dawley rats were randomly divided into the control group, the low, middle and high dose groups, with 10 rats in each group, and the other 10 in vitro experiments.Leonurine group were given leonurine saline suspension, and the control group was given normal saline. Four weeks later, enzyme linked immunosorbent assay was adopted for analysis of the content of nitric oxide in the serum and endothelin-1 in the plasma. The 3 rd mesenteric artery was harvested and stained by hematoxylineosin. Multi Wire Myograph System was used to observe the relaxation effect of leonurine on endotheliumintact and endothelium-denuded third rats mesenteric artery rings, and the relaxation effect with inhibitor of nitric oxide synthase（L-NAME）, soluble guanylate cyclase（s GC） inhibitor（NS-2028） and calcium channel antagonist nifedipine incubated. Results Compared with the control group, the content of nitric oxide（NO） in serum and the content of endothelin-1（ET-1） in plasma of leonurine group decreased. As the dose of leonurine increases, the ET-1 decreased faster. Hematoxylin-eosinstaining showed the blood vessel wall of the Leonurine group was thinner than that of the saline control group, and the effect is dose-dependent. Leonurine can directly relax the endothelium-intact isolated mesenteric artery rings. The relaxation effect of leonurine on the endothelium-denuded isolated mesenteric artery was obvious and with incubation of inhibitor of nitric oxide synthase（L-NAME）, soluble guanylate cyclase（s GC） inhibitor（NS-2028） and calcium channel antagonist nifedipine, the relaxation effect was significantly reduced. Conclusion Leonurineintragastric administration has a protective effect on rat mesenteric artery. The vasodilation effect of leonurine on isolated mesenteric artery rings was concentration dependent and endothelium dependent. This effect may be related to NO-s GC-c GMP signaling pathway and L-type calcium channel.