白桦脂酸改善氧化应激损伤大鼠血管的内皮依赖性舒张功能

Betulinic acid ameliorates impairment of endothelium-dependent relaxation induced by oxidative stress in rat aorta

目的:研究白桦脂酸(betulinic acid,BA)舒张血管效应及抗血管氧化应激损伤的血管保护作用,并探讨其内在机制。方法:取胸主动脉进行离体灌流,用累积加药法观察BA对苯肾上腺素(phenylephrine,PE)预收缩的内皮完整血管环和去内皮血管环的舒张作用,并将血管随机分为正常对照组、BA对照组、H2O2组和BA+H2O2组,并在用PE预收缩后,检测血管环对乙酰胆碱(acetylcholine,ACh)诱导的内皮依赖性舒张反应,血管环张力变化均通过PowerLab生物信号采集系统记录。结果:BA浓度依赖性(10-7mol/L^10-4mol/L)舒张PE(10-6mol/L)预收缩的内皮完整胸主动脉环,pD2值为5.61±0.18,半数有效浓度(EC50)为(2.45×10-6)mol/L;一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAME,10-4mol/L)预处理抑制了该作用,而用吲哚美辛(10-5mol/L)预处理则无抑制作用。但对PE预收缩的去内皮血管BA无明显舒张作用。H2O2(5×10-4mol/L)孵育15 min,能降低ACh(10-9mol/L^10-5mol/L)诱导的血管舒张作用;EC50的BA孵育30min,能抑制H2O2氧化应激损伤所致的血管内皮依赖性舒张功能下降。结论:BA具有内皮依赖性舒张血管作用,BA可以减轻H2O2诱导的大鼠胸主动脉内皮依赖性舒张功能降低,这可能与其降低血管内皮氧化应激,维持血管内皮一氧化氮活性有关。

Objective： To investigate the effect of betulinic acid（BA） on relaxation in isolated rat aortic rings and its antioxidant property on oxidative stress of blood vessels.Methods： Aortic rings were isolated and BA was cumulatively added into organ bath.Isometric tension of endothelium intact or endothelium denuded thoracic aortic rings previously contracted by phenylephrine（PE） was recorded.Then aortic rings were randomly divided into normal control group,BA control group,H2O2 group and BA＋ H2O2 group,after being previously contracted by PE,isometric tension of endothelium-dependent relaxation induced by Ach was recorded.Results： Exposure of intact endothelium rings previously contracted by PE to BA at the concentrations of 10-7 mol/L-10-4 mol/L evoked a significant concentration dependent relaxation,which was inhibited by pretreatment with Nω-nitro-L-arginine methyl ester（L-NAME,10-4mol/L）,but not by indometacin（10-5mol/L）.The pD2 value of BA was 5.24±0.04,and the EC50 value was 2.45×10-6 mol/L.Exposure of endothelium denuded rings previously contracted by PE to BA did not affect the relaxation in isolated aortic rings.ACh induced a dose-dependent relaxation that was weakened by pretreatment with H2O2（5 10-4 mol/L） for 15 min.The EC50 of BA markedly attenuated the inhibition of relaxation induced by H2O2.Conclusions： BA can evoke a concentration-dependent relaxation in aortic rings previously contracted by PE,which may be mediated by NO.And the decrease of endothelium-dependent relaxation in rat aortic rings exposed to H2O2 can be markedly attenuated by BA,which may be mediated by reducing oxidative stress and maintaining the activity of NO in aortic rings.