CAJ | 학술논문

目的：系统比较国产乌司他丁对凝血和抗凝血系统中的凝血因子10、纤溶酶、凝血酶、激肽原酶以及多形核粒细胞弹性蛋白酶活性的抑制效果，为临床研究的剂量选择提供依据。方法设计合成生色底物，分别采用灵敏的荧光检测方法，优化反应过程酶和底物的浓度。采用多点法测定并计算乌司他丁对各种丝氨酸蛋白酶的半数抑制率。结果乌司他丁可以明显抑制多型核粒细胞弹性蛋白酶（ polymorphonuclear leukocyte elastase ，PMNE）和纤溶酶，IC50均低于100 U／mL。对凝血因子Xa 以及激肽原酶抑制均高于1000U／mL，但对凝血酶无抑制作用。结论国产乌司他丁对PMNE的抑制效果最强，与日本同类产品对这几种丝氨酸蛋白酶的抑制效果相似，为其在抗炎、抗凝、促凝及抗休克效果中选择合适的剂量区间提供了可靠数据。
목적：계통비교국산오사타정대응혈화항응혈계통중적응혈인자10、섬용매、응혈매、격태원매이급다형핵립세포탄성단백매활성적억제효과，위림상연구적제량선택제공의거。방법설계합성생색저물，분별채용령민적형광검측방법，우화반응과정매화저물적농도。채용다점법측정병계산오사타정대각충사안산단백매적반수억제솔。결과오사타정가이명현억제다형핵립세포탄성단백매（ polymorphonuclear leukocyte elastase ，PMNE）화섬용매，IC50균저우100 U／mL。대응혈인자Xa 이급격태원매억제균고우1000U／mL，단대응혈매무억제작용。결론국산오사타정대PMNE적억제효과최강，여일본동류산품대저궤충사안산단백매적억제효과상사，위기재항염、항응、촉응급항휴극효과중선택합괄적제량구간제공료가고수거。
Objective To study inhibitory effect of serine protease activity by Ulinastatin in vitro .Methods Different chromogenic peptides were designed and synthesized.Highly sensitive fluorescence detection was performed to optimize the concentration of each serine proteases and their chromogenic substrates.Multi-point method was used for the calculation of half maximal inhibitory concentration of Ulinastatin .ResuIts Ulinastain could inhibit Polymorphonuclear leukocyte elastase ( PMNE ) and plasmin with IC50 lower than 100 U/mL.For factor Xa, and Kallikrein, the IC50 of Ulinastatin was higher than 1000U/mL.No thrombin IC50 could be calculated at the present experiments.ConcIusion Similar to Ulinastatin injection from Japan, domestic Ulinastatin shows the strongest inhibitory effects on PMNE among those serine proteases.As important references, this study gives reliable data for dose range of domestic Ulinastatin in anti-inflammation, coagulation/anti-coagulation and anti-shock therapy.