重组单环刺螠纤溶酶对大鼠急性心肌缺血的保护作用

Protective Effect of Recombinant Urechis Unicinctus Fibrinolytic Enzyme on Rats with Acute Myocarchal Ischemia

目的研究重组单环刺螠纤溶酶对大鼠急性心肌缺血的保护作用。方法重组表达单环刺螠纤溶酶,并通过纤维蛋白平板法测定酶活力,体外抗凝试验检测抗凝效果。建立大鼠急性心肌缺血模型,观察并测定重组单环刺螠纤溶酶对大鼠心肌梗死质量比、血清学生化指标[乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)和天门冬氨酸氨基转移酶(aspartate amino transferase,AST)]、凝血指标[凝血酶原时间(prothrombin time,PT)、部分凝血活酶时间(partial thromboplastin time,APTT)、纤维蛋白原(fibrinogen,FIB)、凝血酶时间(thrombin time,TT)]、组织型纤溶酶原激活物(tissue plasminogen activator,t-PA)及组织型纤溶酶原激活物抑制因子1(tissue plasminogen activator inhibitor,PAI-1)活性的影响。结果与模型组相比,重组单环刺螠纤溶酶能缩小心肌梗死范围,抑制AST、LDH、CK的升高,延长PT、APTT、TT,降低FIB,降低PAI-1活性,升高t-PA活性,均具有显著性差异(P<0.01)。结论重组单环刺螠纤溶酶能明显增强纤溶活性,降低凝血时间,说明其抑制凝血系统、活化纤溶系统的作用机制之一可能是抑制血栓形成、抗心肌缺血。重组单环刺螠纤溶酶可有效预防心肌梗死,此结果可为下一步的临床应用提供一定的理论依据。

OBJECTIVE To investigate the protective effect of recombinant Urechis unicinctus fibrinolytic enzyme on rats with acute myocarchal ischemia.METHODS Recombined and expressed the Urechis unicinctus fibrinolytic enzyme.The fibrinogen plate method was used to estimated enzyme activity and the anticoagulation test was used to detected the anticoagulation effect in vitro.The rat model of acute myocardial ischemia was established to observe and determine the effect of recombinant Urechis unicinctus fibrinolytic enzyme on the weight ratio of myocardial infarction,serum biochemical indexes as lactate dehydrogenase(LDH),creatine kinase(CK),aspartate amino transferase(AST),blood coagulation index as prothrombin time(PT),partial thromboplastin time(APTT),fibrinogen(FIB),thrombin time(TT),activity of tissue plasminogen activator(t-PA)and tissue plasminogen activator inhibitor-1(PAI-1).RESULTS Compared with the model group,recombinant Urechis unicinctus fibrinolytic enzyme reduced the range of myocardial infarction,inhibited the increase of AST,LDH and CK,prolonged PT,APTT,TT,reduced FIB,increased t-PA activity and reduced PAI-1 activity,all had significant differences(P<0.01).CONCLUSION Recombinant Urechis unicinctus fibrinolytic enzyme can obviously enhance the fibrinolysis activity and reduce the coagulation time,which suggested that its inhibition of coagulation system and activation of fibrinolytic system may be one of its mechanisms for inhibiting thrombosis and anti myocardial ischemia.Recombinant Urechis unicinctus fibrinolytic enzyme can effectively prevent myocardial infarction,which can provide a theoretical basis for the next clinical application.