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W ortm annin 是肌醇磷脂3激酶的不可逆抑制剂.用比浊法分析血小板聚集;肌醇磷脂用32 P磷酸钠标记,用氯仿和甲醇抽提,用 T L C和放射自显影分析,研究了 W ortm annin 对凝血酶诱导的人血小板聚集和磷脂酰肌醇三磷酸( P I P3)累积的影响.结果显示, W ortm annin 对凝血酶(500 U/ L)诱导的人血小板聚集有抑制作用,这种抑制作用在一定范围内呈剂量依赖关系(20~80μm ol/ L).凝血酶(500 U/ L)诱导人血小板 P I P3 的累积, W ortm annin 对此累积有抑制作用,这种抑制作用在一定范围内呈剂量依赖关系(40~160 μm ol/ L).结果提示: W ortm annin 可能是潜在的抗血小板药物,抑制凝血酶诱导的人血小板聚集主要与其抑制 P I P3 的累积有关.结果也提示,肌醇磷脂3激酶在血小板活化中起重要作用.
W ortm annin is an irreversible inhibitor of phosphoinositide 3-kinase. Platelet aggregation was assayed by turbidimetry. Phosphoinositide was labeled with 32P-sodium phosphate and extracted with chloroform and methanol. TcL and autoradiography were used to analyze the effect of Wortm annin on thrombin-induced platelet aggregation and Effect of phosphatidylinositol triphosphate (P I P3) accumulation. The results showed that Wortm annin inhibited thrombin (500 U / L) -induced human platelet aggregation in a dose-dependent manner (20-80 μmol / L). Thrombin (500 U / L) induced the accumulation of P I P3 in human platelets, and Wortmannin had a cumulative effect of inhibiting this effect in a dose-dependent manner (40-160 μmol / L). The results suggest that Wortm annin may be a potential anti-platelet drug, and inhibition of thrombin-induced human platelet aggregation is mainly associated with its inhibition of P I P3 accumulation. The results also suggest that inositol phospholipid 3 kinase plays an important role in platelet activation.