决明子提取物对大鼠主动脉扩血管作用的机制

Effects of Semen Cassiae Extracts on Vasorelaxation and Its Mechanisms in Rat Aorta

背景决明子在动物实验和临床实践中发现有降压作用,但降压机制的研究未见报道。目的研究决明子提取物的扩血管作用并探讨其机制。方法制备SD大鼠有内皮和去内皮胸主动脉环,分别预先做氯化钾和去氧肾上腺素(PE)处理,制备量效曲线,观察决明子提取物0.1及1.0mg/L在有内皮、无内皮细胞,有钙及无钙等不同条件下,对氯化钾和PE量效曲线的影响(n=6),以及血管紧张素Ⅱ(AngⅡ)引起人脐静脉内皮细胞(HUVEC)一氧化氮、总一氧化氮合酶(TNOS)和诱生型一氧化氮合酶(iNOS)的变化。化学法检测细胞上清液中一氧化氮含量,重氮法检测细胞匀浆中TNOS和iNOS的活性(n=7)。结果决明子提取物能使有内皮血管环氯化钾缩血管量效曲线向右下移,对去内皮血管环氯化钾量效曲线无明显影响;对去内皮和有内皮血管环PE缩血管量效曲线均有明显向右下移作用;对无钙克氏液中PE引起的血管收缩无影响。溶液Ca2+分别为1.1和2.2mmol/L时,决明子1.0及0.1mg/L都有减少PE引起血管收缩的作用。决明子还能对抗AngⅡ(10-6mol/L)引起内皮细胞培养液NO下降,iNOS增高的作用。结论决明子提取物的扩血管作用可能与抑制受体操纵性钙通道开放、调节血管内皮细胞iNOS和一氧化氮释放有关。

Background Semen Cassiae decreases blood pressure in hypertensive animals and patients,but the mechanisms are not clear.Objective To study the vasodilative effect of Semen Cassiae extracts and explore possible mechanisms involved.Methods The aortic rings with endothelium or de-endothelium from Sprague Dawley rats were isolated and suspended in organ chambers and pretreated with different doses of potassium chloride （KCl） or phenylephrine hydrochloride （PE） for the measurement of the contractile force.Semen Cassiae extracts of 0.1 and 1.0 mg/L （n=6） were added in the presence of endothelium or de-endothelium as well as in the presence of calcium or calcium-free.The effects of Semen Cassiae extracts on nitric oxide （NO） in cell super natant and total nitric oxide synthase （TNOS） and inducible nitric oxide synthase （iNOS） activities in human umbilical vein endothelial cells（HUVECs） after Ang Ⅱ（10^-6 mol/L） were detected by chemical and diazo assay respectively （n=7）.Results Semen Cassiae extracts inhibited the contraction-response curve by KCl in aortic rings with endothelium,but not without endothelium,whereas,significantly weakened the contraction-response curve for PE in both aortic rings with endothelium and without endothelium.Semen Cassiae extracts could not affect the vasoconstriction induced by PE in calcium-free Krebs,while the extracts of 1.0 and 0.1 mg/L obviously decreased the vasoconstriction induced by PE after replenishing Ca^2＋ of 1.1 and 2.2 mmol/L.Furthermore,Semen Cassiae extracts antagonize the NO reduction and iNOS increment caused by Ang Ⅱ in HUVECs.Conclusion The vasodilative effects of Semen Cassiae extracts may be partially related to inhibiting receptor-controlled calcium channel on vessels and regulating the secretion of NO and iNOS from vascular endothelial cells.