豆豉纤溶酶Subtilisin FS33的溶栓作用及其机制的研究  

STUDIES ON FIBRINOLYTIC FUNCTION OF SUBTILISIN AND ITS MECHANISM

作　　者：王成涛[1,2] 郑杰[3] 籍保平[3] 曹雁平[1] 孙宝国[1] 刘旭东 

机构地区：[1]北京工商大学化学与环境工程学院 [2]中国农业大学食品与营养工程学院,北京100037 [3]中国农业大学食品与营养工程学院 [4]莱州出入境检验检疫局

出　　处：《营养学报》2007年第6期600-604,共5页Acta Nutrimenta Sinica

基　　金：国家重点基础研究发展计划973项目(No.2007CB707802)

摘　　要：目的:通过动物血栓模型研究豆豉纤溶酶Subtilisin FS33对机体凝血系统和纤溶系统的影响及其作用机制。方法:Subtilisin FS33与不同处理的血凝块37℃恒温孵育,测定血凝块溶解时间(CLT);利用FeCl3氧化损伤动脉内膜法制造大鼠血栓模型,不同剂量的Subtilisin FS33、尿激酶和生理盐水分别给于受试大鼠。结果:Subtilisin FS33对80℃加热处理血凝块的水解明显慢于未经加热处理组,提示Subtilisin FS33在缺乏内源性纤溶因子的情况下,仍能溶解血栓纤维蛋白。Subtilisin FS33高剂量组和尿激酶组,静脉注射15min和1h后,与机体凝血功能相关的血液学指标活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)和凝血时间(CT)明显延长,机体的纤溶酶活力显著增高,血栓降解产物FDP含量升高,D-二聚体均呈阳性,而机体优球蛋白溶解时间(ELT)值明显降低;Subtilisin FS33低剂量组的APTT、PT、TT也比生理盐水组相应延长,但差异性大多未达到显著水平。病理组织切片结果表明,静注Subtilisin FS33后,大鼠肺静脉和肾小球毛细血管等无明显血栓,而生理盐水对照组的大鼠肺静脉等仍存在少量丝状纤维物。结论:Subtilisin FS33在体内和体外均具有明显的降解血栓纤维蛋白的能力,增强机体的纤溶活性、提高抗凝能力是其溶栓作用的主要途径。Objective： To evaluate the effect how Subtilisin FS33 affect thrombotic and fibrinolytic systems in vitro and in vivo. Method： Activity of Subtilisin FS33 was measured by clot liquefaction time （CLT）. On the model of 10% FeC13 induced thrombi of carotid arteries in rats, various doses of Subtilisin FS33 were injected to the rats, and the fibrinolytic effect was observed. Results： 0.5 g of the unheated blood clots gradually dissolved within 45 min, whereas the blood clots heated at 80℃ for 30 rain dissolved within 3 h. This indicated that the enzyme was able to degrade blood clots in the absence of endogenous fibrinolytic factors. The experiment in vivo indicated that high dose subtilisn group could significantly prolong CT （coagulation time ）, PT （prothrombin time）, TT （thrombin time ）, APTT （activated partial thromboplastin time） , reduce ELT （euglobulin lysis time） , decrease the content of FIB （fibrinogen） , increase the content of FDP （fibrinogen degradation products）. D-dimer of all experimental groups was positive. The venous thrombus in lung and kidney was dissolved totally or partly as observed by pathological section. Conclusion： Both thrombolytic effects of Subtilisin FS33 in vitro and in vivo were significant and the mechanisms might be associated with enhancing anticoagulation activity and fibrinolysis.

关 键 词：SUBTILISIN FS33 大鼠血栓模型 纤溶活性 溶栓剂 作用机制 

分 类 号：R151[医药卫生—营养与食品卫生学]