目的：研究白藜芦醇（Resveratrol, RES）对离体人肺内小动脉血管张力的影响及其机制。方法显微镜下分离直径为1~1.5 mm的人肺内小动脉，制备成1.8~2.0 mm的血管条，使用微血管张力测定技术，分别给予血管收缩剂血栓素A2受体激动剂（U46619）、内皮素-1（ET-1）、60 mmol/L高钾溶液使血管产生持续性收缩，张力平稳后，采用累计加药法加入白藜芦醇，观察不同浓度白藜芦醇对预收缩的人肺内小动脉张力的影响；同时观察去内皮，以及加入L-NAME、吲哚美辛预孵育血管后，白藜芦醇能否使预收缩的血管舒张。白藜芦醇舒张实验同时用等体积的药物容积二甲亚砜（DMSO）作为对照。结果 RES能呈浓度依赖性舒张U46619（100 nmol/L）、ET-1（30 nmol/L）、60 mmol/L高钾预收缩内皮完整的人肺内小动脉，pD2分别为3.82±0.20，3.84±0.57，3.68±0.27，其最大舒张率（Emax）分别为（99.58±0.83）%，100%，（99.65±0.98）%；用L-NAME预孵育30 min内皮完整的人肺内小动脉血管环，在浓度100μmol/L时，同未加L-NAME孵育的血管环比较，两者之间具有统计学差异（P<0.05）；而用吲哚美辛预孵育30 min内皮完整的人肺内小动脉环不影响白藜芦醇的舒张作用，去除血管环的内皮亦同样不影响白藜芦醇的舒张作用。结论白藜芦醇具有浓度依赖性的舒张离体人肺内小动脉的作用，且无明显的内皮依赖性，其作用机制可能与促进NO的释放有关。%Objective To determine the effect of resveratrol on constrictions of isolated human intrapulmonary arteries and its mechanisms. Methods Intrapulmonary arteries (1-1.5 mm in diameter) were dissected and cut into rings (1.8-2.0 mm in length) under microscope, and were then mounted in a Multi Myograph system. The rings were stimulated with 100 nmol/L U46619, 30 nmol/L endothelin-1, or 60 mmol/L KCl to produce sustained contraction of the intrapulmonary arteries, after which resveratrol was applied cumulatively. Endothelium denudation, L-NAME and indomethecin were used to investigate the effect of resveratrol on constrictions of the isolated arteries, suing DMSO as the control. Results Resveratrol induced concentration-dependent relaxations in endothelium-intact rings that contracted in response to stimulations with U46619, ET-1 and KCl, with pD2 of 3.82 ± 0.20, 3.84 ± 0.57, and 3.68 ± 0.27, Emax of (99.58 ± 0.83)%, 100%, and (99.65 ± 0.98)%, respectively. Treatment of the arterial rings with the eNOS inhibitor L-NAME, but not with indomethecin or endothelium denudation, obviously affected the relaxant effects of resveratrol. Conclusion Resveratrol can concentration-dependently produce relaxant effect on human intrapulmonary arteries independent of the endothelium possibly by promoting synthesis and release of NO.
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