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血小板聚集是正常止血的要素,并依赖于膜糖蛋白Ⅱ_b/Ⅲ_a(GPⅡ_a/Ⅲ_a)复合物与血浆粘附糖蛋白(包括纤维蛋白原 von Willebrand 因子和 fibronectin)的相互作用。研究 GPⅡ_b/Ⅲ_a 受体与纤维蛋白结合确定了在介导其自身与 GP Ⅱ_b/Ⅲ_a 接触的纤维蛋白分子中存在两种不同的氨基酸序列。其中一种序列是 Arg-Gly-Asp(RGD),该序列不仅出现在纤维蛋白 Aα链中,也出现在 fibronectin 和 von Willebrand 因子中。为了阐明其生物学效应本文合成了RGDS,并进行了与抗栓有关的生物学评价。本研究提供的数据证实 RGDS 明显抑制 PAF或 ADP 诱发的血栓形成(对 PAF 诱导的血小板聚集抑制率为67%,RGDS 浓度为9.6×10~(-7)mol/L;对 ADP 诱导的血小板聚集抑制率为87%,RGDS 浓度为9.6×10~(-7)mol/L)。该观察与 RGDS 延缓血栓形成的发现相符。虽然 RGDS 对 ADP 比对 PAF 更敏感但它对 PAF 的抑制仍十分明显这些结果均属首次报道。本研究进一步揭示了 RGDS 有舒血管作用,而且它对大鼠主动脉肌条的舒张作用不可忽视(与对照相比1×10~(-5)mol/L 的 RGDS 在 NE 处理的鼠动脉肌条上的舒张幅度为8.08±5.0%,P<0.05)。对组织内 cGMP 的累积水平(与对照相比1±10~(-5)mol/L 的RGDS 引起 cGMP 水平增高4.68±1.9pmol/mg,P<0.05)研究结果表明,提高体内 cGMP 的水平可能是 RGDS 发挥生物学作用的机制之一。RGDS 的舒血管和抗血小板聚集两种作用均可作为设计与合成新型抗栓剂的实验依据。
Platelet aggregation is a normal hemostatic factor and is dependent on the interaction of the membrane glycoprotein II_b / III_a (GPⅡ_a / Ⅲ_a) complex with plasma adherent glycoproteins, including von Willebrand factor and fibronectin. The study of the binding of GPII_b / III-a receptor to fibrin confirmed the existence of two different amino acid sequences in the fibrin molecule that mediates its own association with GP II_b / III-a. One of the sequences is Arg-Gly-Asp (RGD), which appears not only in the fibrin Aα chain, but also in fibronectin and von Willebrand factor. In order to clarify its biological effects, RGDS was synthesized in this paper and biological evaluation related to antithrombotic activity was performed. The data provided in this study confirm that RGDS significantly inhibits PAF or ADP-induced thrombosis (PAF-induced platelet aggregation inhibition was 67%, RGDS concentration 9.6 × 10 -7 mol / L, ADP-induced platelet aggregation The inhibition rate was 87%, RGDS concentration was 9.6 × 10 ~ (-7) mol / L). This observation is consistent with the finding that RGDS delays thrombosis. Although RGDS is more sensitive to ADP than to PAF, its effect on PAF is still evident. These results are the first to be reported. This study further revealed that RGDS has a vasodilating effect and its vasodilating effect on rat aortic strips can not be ignored (1 × 10 ~ (-5) mol / L RGDS in the NE-treated murine arterial muscle The amplitude of relaxation was 8.08 ± 5.0%, P <0.05). The level of cGMP accumulation in the tissue (cGMP level increased by 1. ± 10 -5 mol / L compared with the control was 4.68 ± 1.9 pmol / mg, P <0.05) showed that increasing the level of cGMP in vivo may It is one of the mechanisms by which RGDS plays a biological role. RGDS of vasodilatation and anti-platelet aggregation can be used as two experimental basis for the design and synthesis of new antithrombotic agents.