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目的:探讨贵州豆豉溶栓激酶DCK(DCK酶)的体内溶栓抗栓作用及其相关机制。方法:雄性昆明小鼠随机分为模型组,尿激酶(150 U·g~(-1))组,DCK酶低、中、高剂(150,300,450 U·g~(-1))组,ip 7 d,每日1次,第7天给药30 min后,各组小鼠ip 0.8%角叉菜胶,继续每天给药,观察尾部血栓的变化,于24,36 h游标卡尺测量鼠尾长度和血栓长度,计算血栓形成率和血栓形成相对长度。Wistar大鼠随机分为模型组,尿激酶(100 U·g~(-1))组,DCK酶低、中、高剂量(100,200,300 U·g~(-1))组,ip 10d,每日1次。第10天给药30 min后,水合氯醛溶液麻醉大鼠,分离右颈总动脉、左颈外静脉,构建右颈总动脉-左颈外静脉旁路循环,比较该旁路循环异物所致血栓湿重。新西兰大耳白兔随机分为模型组,尿激酶(38 U·g~(-1))组,DCK酶低、中、高剂量(38,76,114 U·g~(-1))组,耳缘静脉注射给药,给药1 h后耳缘静脉采血,进行凝血酶原时间(PT),活化部分凝血活酶时间(APTT),凝血酶时间(TT),纤维蛋白原(FIB),优球蛋白溶解时间(ELT),纤维蛋白(原)降解产物(FDP)的检测。结果:与模型组比较,DCK酶组在24,36 h各组小鼠鼠尾血栓形成相对长度均明显减少(P<0.05,P<0.01);DCK酶高、中剂量组的旁路循环血栓湿重明显减少(P<0.05,P<0.01)。DCK酶高、中剂量组的PT,APTT,TT时间明显延长(P<0.05,P<0.01),DCK酶高、中剂量组FIB明显减少(P<0.05,P<0.01),DCK酶高、中剂量组ELT的水平明显降低(P<0.05),DCK酶组FDP含量均增加,中剂量组明显增加(P<0.05)。结论:DCK酶具有良好的体内溶栓抗栓作用。
Objective: To investigate the in vivo thrombolysis and antithrombotic effect of DCK enzyme and its related mechanism. Methods: Male Kunming mice were randomly divided into model group, 150 U · g ~ (-1) Urokinase group, 150, 300, 450 U · g ~ (-1) d, once a day, on the seventh day after administration for 30 min, mice in each group ip 0.8% carrageenan, continue daily administration, observe the changes of caudal thrombosis, measuring the rat tail length at 24 and 36 h vernier caliper Thrombus length, calculated thrombosis rate and relative length of thrombosis. Wistar rats were randomly divided into model group, urokinase (100 U · g -1) group, DCK enzyme group low, medium and high doses (100, 200, 300 U · g -1) 1 time. On the 10th day after administration, the chloral hydrate solution was anesthetized in rats, the right common carotid artery and the left external jugular vein were isolated and the right common carotid artery-left external jugular vein bypass was established. Thrombus wet weight. New Zealand white rabbits were randomly divided into model group, urokinase (38 U · g -1) group, DCK enzyme low, medium and high doses (38, 76, 114 U · g -1) The marginal venous blood was collected 1 h after administration, and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB) Globulin lysis time (ELT), fibrin (prot) degradation products (FDP) detection. Results: Compared with model group, the relative length of rat tail thrombosis in DCK enzyme group was significantly decreased at 24 and 36 h (P <0.05, P <0.01) Wet weight decreased significantly (P <0.05, P <0.01). Compared with DCK group, the levels of PT, APTT and TT in high and medium dose DCK groups were significantly prolonged (P <0.05, P <0.01) The level of ELT in the middle dose group was significantly lower (P <0.05). The content of FDP in the DCK enzyme group was increased and the middle dose group was significantly increased (P <0.05). Conclusion: DCK enzyme has a good thrombolytic and antithrombotic effect in vivo.