原花青素舒张家兔离体肺动脉的研究

Vasorelaxant effects of procyanidins on rabbit pulmonic ring in vitro

目的：研究葡萄籽提取物原花青素（PC）对家兔离体肺动脉血管的舒张作用及机制。方法：采用家兔离体肺动脉平滑肌标本，以去甲肾上腺素（NA）预收缩后，给予PC（0．625，1．25，2．5mg·L^-1），观察其舒张血管的量效关系；并分为对照组、PC组、PC＋吲哚美辛（1×10^-5mg·L^-1）、PC＋普萘洛尔（1×10^-5mg·L^-1）、PC＋左旋硝基精氨酸（1×10^-5mg·L^-1）、PC＋甲烯蓝（1×10^-5mg·L^-1）和PC＋去内皮细胞7组，探讨PC舒张血管的机制；用PC（20mg·L^-1）温育标本后，观察PC对NA（1×10^-8-1×10^-5mg·L^-1），KCl（6．3～100mmol·L^-1）和CaCl2（1×10^-5～1×10^-5mg·L^-1）量效曲线的影响。结果：PC能明显舒张肺动脉血管，并有量效关系（r=0．69，P〈0．01）；去除血管内皮、L—NNA或MB可抑制PC的舒张作用，但吲哚美辛和普萘洛尔无影响；PC能压低NA，KCl和CaCl2的量效收缩曲线，三者的pD2分别由对照的（7．57±2．41），（1．74±1．19），（3．72±1．88）降低为（6．47±1．42），（1．07±1．12），（3．17±1．55）；PC也能抑制NA引起的第I时相收缩，对CaCl2引起的第Ⅱ时相收缩无影响。结论：PC舒张肺动脉的作用是内皮依赖性，且与NO／cGMP介导有关；也可能是拮抗ROC和PDC通道，降低胞浆Ca^2＋而舒张血管。

Objective： To study the vasorelaxant effect of procyanidin （PC） extracted from grape seeds on rabbit thoracic pulmonic rings in vitro. Method： Rabbits thoracic pulmonic rings were isolated, pre-contracted with noradrenalin （NA） and their responses to different concentrations of PC were investigated. The effects of endothelium and different signaling pathway inhibitors on PC-induced relaxation, including nitric oxide synthase inhibitor N^w-nitro-L-arginine （ L-NNA）, methylene blue （ MB）, prostaglandin synthase inhibitor indomethacin （Indo） and blockage of the adrencrgic β-receptor propranolol （Prop）, were also assessed. Result： PC change the resting tension of rabbit＇s pulmonic rings but caused an obvious dose-dependent relaxation in 1 × 10^-6 mol · L^-1 NA precontracted pulmonic rings （ r = 0. 69, P 〈 0. 01 ）. The relaxant effect of PC was significantly reduced by removal of endothelium or by treatment with either 1 × 10^-4 mol · L^-1 L-NNA or 1 × 10^-2 mol L^-1 MB, but not by treatment with prostaglandin synthase inhibitor or blockage of the adrenergic β-receptor. In addition, PC （20 mg · L^-1 ） dropped the dose-effect curves of NA, KCl and respectively on pulmonic rings denuded endothelium. PC can also inhibit the vasoconstriction caused by NA in the first phase, but has no impact on the constriction induced by CaCl2 in the second phase. Conclusion： PC has an endothelium-dependent vasorelaxation on isolated rabbit g pulmonic rings, which is possibly mediated by nitric oxide （NO） pathways and blockage of receptor operated and voltage dependent calcium channels.