豆豉溶栓激酶DCK的体内溶栓抗栓作用

Douchi Fibrinolytic Kinase DCK Thrombolysis and Antithrombotic Function in vivo

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 study Guizhou Douchi fibrinolytic kinase DCK （DCK enzyme） thrombolysis and antithrombotic function in vivo. Method： Male Kunming mice were randomly divided into model group, urokinase control group （150 U·g-1 ）, DCK enzyme low, medium and high dose group （150, 300, 450U·g-1 ）, ip 7 d, once a day, each group were injected 0.8% carrageenan to build the thrombus model in tail after 30 minutes 7 days administration. Tail thrombosis was observed and the mice tail length and the length of thrombus were measured at 24, 36 h. Thrombus formation rate and thrombosis relative length were calculated. Wistar rats were randomly divided into model group, urokinase control group （100U·g-1） and DCK enzyme low, medium and high dose group （100, 200, 300U·g-1） , ip 10 days, once a day. Rats were anesthetized by chloral hydrate solution after 30 minutes the 10 days treatment, the right common carotid artery and left external jugular vein were separated to build the right common carotid artery-left external jugular vein bypass. Thrombus wet weight were get in the bypass circulation. New Zealand white rabbits were randomly divided into model group, urokinase control group （38U·g-1） , DCK enzyme low, medium and high dose group （38, 76, 114U·g-1） by ear vein injection administration, blood sampling of ear border vein were administered after 1 h to detect prothrombin time （PT）, activated partial thromboplastin time （APTT）, thrombin time （TT）, human fibrinogen （FIB）, euglobulin clot lysis time （ELT） and fibrin （-ogen） degradation products （FDP）. Result： Compared with the model group, DCK enzyme group at 24, 36 h tail thrombosis formation relative length were reduced （P 〈 0.01, P 〈 0.05）, DCK enzyme of high, middle dose group of bypass thrombus wet weight were reduced （P 〈 0.01, P 〈 0.05）. The PT, APTT, TT time extended with significant difference （P 〈0.01, P 〈 0.05） , the FIB of high DCK enzyme group was reduced （P 〈0.05, P 〈0.01 ） , high DCK enzyme and middle dose group of ELT was decreased （P 〈 0.05） , and DCK enzyme in each experimental group FDP content were increased, the middle dose group increased （P 〈 0.05 ）. Conclusion： DCK enzyme has a certain thrombolysis and antithrombotic function in vivo.