2019 年第 10 期 第 14 卷

不同剂量尿激酶对脓毒症性凝血紊乱大鼠干预作用的实验研究

Effect of urokinase on septic coagulopathy in rats: an experimental study

作者：宋晓敏吴阳曾俊杰

英文作者：

单位：330002南昌,中国人民解放军联勤保障部队第九〇八医院重症医学科

英文单位：

关键词：脓毒症；尿激酶；凝血紊乱；内毒素

英文关键词：

• 摘要：

• 【摘要】目的    探讨低剂量与高剂量尿激酶对脓毒症性凝血紊乱大鼠的干预作用。方法    选择无特定病原体级大鼠80只，雌雄各40只,随机分为4组，每组20只。A组不造模，尾静脉输注0.9%氯化钠注射液；B组尾静脉输注0.9%氯化钠注射液+内毒素制作脓毒症性凝血紊乱大鼠模型；C组制作脓毒症性凝血紊乱大鼠模型后给予低剂量尿激酶干预；D组制作脓毒症性凝血紊乱大鼠模型后给予高剂量尿激酶干预；比较4组大鼠给药1 h后凝血及纤溶指标水平和C、D组大鼠给药1、2、3、4、5 h共5个时点凝血及纤溶指标以及血清丙氨酸转氨酶和肌酐水平。观察C、D组大鼠肝、肾、肺组织病理改变情况。结果    D组大鼠给药1 h后凝血酶时间（TT）、凝血酶原时间（PT）、纤维蛋白原降解产物（FDP）、D-二聚体水平均高于A、B、C组［（34.4±2.8）s比（29.5±0.5）、（30.1±0.4）、（32.5±1.5）s；（13.5±3.3）s比（9.8±0.3）、（11.3±0.3）、（11.3±1.4）s；（3.7±0.4）μg/L比（1.1±0.3）、（1.6±0.3）、（2.1±0.3）μg/L；（2.4±0.3）mg/L比（0.8±0.5）、（1.2±0.4）、（1.6±0.3）mg/L］，纤维蛋白原（FIB）、活化部分凝血活酶时间（APTT）水平均低于A、B、C组［（1.6±0.5）g/L比（2.0±0.4）、（1.7±0.5）、（1.9±0.3）g/L；（15.4±0.6）s比（17.0±1.5）、（18.4±1.3）、（21.2±0.3）s］（均P＜0.05）。C组和D组大鼠给药5 h后TT、PT、APTT、FDP、D-二聚体、丙氨酸转氨酶和肌酐水平均高于给药1、2、3、4 h，FIB水平均低于其他时点（均P＜0.05），而C组与D组相同时点血清丙氨酸转氨酶和肌酐水平比较差异均无统计学意义（均P＞0.05）。给予尿激酶后，C、D组大鼠肝、肾、肺组织均未见明显病理改变。结论    使用低剂量的尿激酶可使脓毒症性凝血紊乱大鼠凝血功能及纤溶功能有所改善，且不存在出血倾向；而高剂量的尿激酶可改善凝血及纤溶功能，但可能存在出血倾向。

• 【Abstract】Objective    To investigate the effects of low and high dose urokinase on sepsis-induced coagulation disorder in rats. Methods    Eighty rats, 40 males and 40 females, were randomly divided into 4 groups, with 20 rats in each group. Group A was injected with 0.9% sodium chloride via caudal vein. Group B was made septic coagulopathy model by 0.9% sodium chloride+endotoxin injection via caudal vein. Group C was made septic coagulopathy model and treated with low dose urokinase. Group D was made septic coagulopathy model and treated with high dose urokinase. Coagulation and fibrinolysis indexes were detected at 1 h after drug administration in 4 groups. Coagulation and fibrinolysis indexes, serum levels of alanine transaminase and creatine were detected at 1, 2, 3, 4, 5 h after drug administration in group C and D. Pathological changes of liver, kidney and lung were observed in group C and D. Results    At 1 h after drug administration, levels of thrombin time, prothrombin time, fibrinogen degradation product and D-dimer in group D were higher, levels of fibrinogen and activated partial thromboplastin time were lower than those in group A, B, C［（34.4±2.8）s vs （29.5±0.5）,（30.1±0.4）,（32.5±1.5）s； （13.5±3.3）s vs （9.8±0.3）,（11.3±0.3）,（11.3±1.4）s； （3.7±0.4）μg/L vs （1.1±0.3）,（1.6±0.3）,（2.1±0.3）μg/L； （2.4±0.3）mg/L vs （0.8±0.5）,（1.2±0.4）,（1.6±0.3）mg/L； （1.6±0.5）g/L vs （2.0±0.4）,（1.7±0.5）,（1.9±0.3）g/L； （15.4±0.6）s vs （17.0±1.5）,（18.4±1.3）,（21.2±0.3）s］(all P<0.05). In group C and D, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen degradation product, D-dimer, alanine transaminase and creatine levels at 5 h were higher and fibrinogen level was lower than those at 1, 2, 3, 4 h after administration（all P＜0.05). There were no significant differences of serum alanine transaminase and creatine levels between group C and D(all P>0.05). No obvious pathological change was observed in liver, kidney and lung tissues in group C and D. Conclusion    Low dose urokinase can improve coagulation and fibrinolysis function in rats with sepsis-induced coagulation disorder and does not lead to increased bleeding risk; high dose urokinase may increase bleeding risk.