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原花青素对离体肺动脉血管张力的影响

     

摘要

BACKGROUND: Procyanidins is a kind of polyphenol compounds in regnum vegetable, which is composed of different quantities of catechin and epicatechin. Studies show that procyanidins plays a role on protecting vascular endothelium, scavenging free radicals, resisting platelet aggregation, and reducing capillary permeability. Thus, procyanidins has obviously functions of reducing blood pressure, anti-oxidant activity, anti-edema, preventing coronary heart disease and atherosclerosis. OBJECTIVE: To study the vasorelaxant effect of procyanidins on pulmonic rings and its mechanisms. METHODS: Rabbit thoracic pulmonary arteries were isolated. Pre-contracted with noradrenalin (1×10-6 mol/L) and their responses to different concentrations of procyanidins (0.625, 1.25, 2.5 mg/L) were investigated. After removal of the endothelium of pulmonary artery smooth muscle, the effects of different signaling pathway inhibitors on procyanidins-induced relaxation, including nitric oxide synthase inhibitor Nω-Nitro-L-arginine (1×10-4 mol/L), methylene blue (1×10-5 mol/L), prostaglandin synthase inhibitor indomethacin (1×10-5 mol/L) and blockage of the adrenergicβ-receptor propranolol (1×10-5 mol/L), were also assessed. RESULTS AND CONCLUSION: (1) Procyanidins did not change the resting tension of rabbit’s pulmonic rings, but caused an obvious dose-dependent relaxation in 1×10-6 mol/L noradrenalin-precontracted pulmonic rings (r=0.69, P < 0.001). (2) The relaxant effect of procyanidins was significantly reduced by removal of endothelium or by treatment with either Nω-Nitro-L-arginine or methylene blue, but not by treatment with prostaglandin synthase inhibitor or blockage of the adrenergic β-receptor. (3) Procyanidins (20 mg/L) dropped the dose-effect curves of noradrenalin, KCl and on pulmonic rings denuded endothelium. Moreover, affinity index of noradrenalin, KCl and CaCl2 decreased (P < 0.01). (4) Procyanidins also inhibited the vasoconstriction caused by noradrenalin in the first phase, but had no impact on the constriction induced by CaCl2 in the second phase. (5) Procyanidins has an endothelium-dependent vasorelaxation on isolated rabbit’s pulmonic rings, which is possibly mediated by nitric oxide/cyclic guanosine monophosphate pathways. Procyanidins blocked receptor-operated and voltage-dependent calcium channels to reduce intracel ular Ca2+, and induced vasorelaxation.%背景:原花青素是广泛存在于植物界中的一类多酚化合物,由不同数量的儿茶素或表儿茶素缩合而成,有保护血管内皮、清除自由基、抗血小板聚集、降低毛细血管通透性、起到降低血压、抗氧化活性、抗水肿、防止冠状动脉粥样硬化性心脏病和动脉粥样硬化等作用。目的:观察原花青素对肺动脉环的舒张作用及机制。  方法:家兔离体肺动脉环为标本,以去甲肾上腺素(1×10-6 mol/L)预收缩肺动脉环后给予0.625,1.25,2.5 mg/L 原花青素观察其张力变化。再将不同浓度原花青素干预的家兔离体肺动脉平滑肌去除血管内皮、给予一氧化氮合酶抑制剂左旋硝基精氨酸(1×10-4 mol/L)、甲烯蓝(1×10-5 mol/L)、环氧酶抑制剂吲哚美辛(1×10-5 mol/L)和β肾上腺素能受体阻断剂普萘洛尔(1×10-5 mol/L),探讨它们对血管张力的影响。  结果与结论:①原花青素对肺动脉环静息张力无明显影响,但不同剂量的原花青素可使1×10-6 mol/L去甲肾上腺素预收缩血管产生明显舒张,并呈量效依赖性(r=0.69,P <0.001)。②去除血管内皮、左旋硝基精氨酸和甲烯蓝均可减弱原花青素舒张血管的作用,但吲哚美辛和普萘洛尔无影响。③20 mg/L原花青素能明显压低去除内皮细胞肺动脉血管的去甲肾上腺素、KCl和CaCl2的量效收缩反应曲线,且去甲肾上腺素、KCl和CaCl2的亲和力指数降低(P <0.01)。④原花青素能抑制去甲肾上腺素引起的第Ⅰ时相收缩,而对CaCl2引起的第Ⅱ时相收缩无影响。⑤实验结果表明原花青素对肺动脉的舒张效应是内皮依赖性的,与NO/cGMP介导有关,可拮抗受体依赖性钙通道和电压依赖性钙通道而降低细胞内Ca2+引起血管舒张。

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