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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (4): 369-374.doi: 10.12047/j.cjap.5994.2020.079

• 研究论文 • 上一篇    下一篇

重组葡激酶对小型猪冠脉血栓的溶栓作用研究*

李光1,2, 方晓兰1, 任仲2, 李克强2, 周松辉2, 胡道奇2, 吴刚强2, 王太林2, 李卫平1△   

  1. 1.岳阳职业技术学院, 岳阳 414000;
    2.湖南康润药业股份有限公司, 岳阳 414000
  • 收稿日期:2019-12-15 修回日期:2020-06-16 发布日期:2020-11-09
  • 通讯作者: Tel: 13575002486; E-mail: 1307878066@qq.com
  • 基金资助:
    *国家战略性新兴产业蛋白质生物药和疫苗发展专项(【2014】2572); 湖南省自然科学基金(2019JJ70006);湖南省教育厅科研基金 (16C1638);湖南省哲学社会科学基金(16YBA347)

Thrombolytic effects of recombinant staphylokinase on coronary thrombosis in miniature pigs

LI Guang1,2, FANG Xiao-Lan1, REN Zhong2, LI Ke-qiang2, ZHOU Song-hui2, HU Dao-qi2, WU Gang-qiang2, WANG Tai-lin2, LI Wei-ping1△   

  1. 1. Yueyang Vocational and Technical College, Yueyang 414000;
    2. Hunan Kangrun Pharmaceutical Co., Ltd., Yueyang 414000, China
  • Received:2019-12-15 Revised:2020-06-16 Published:2020-11-09

摘要: 目的: 评价重组葡激酶的溶栓效力,并与相同作用方式的重组链激酶进行比较。方法: 30只中国实验小型猪分成5组,分别为溶剂对照组、阳性药对照组和三个重组葡激酶组,每组6只,采用麻醉动物、手术开胸、直流电刺激形成冠脉血栓;在冠脉血栓形成30 min后开始静脉给药,采用先推注、再蠕动泵恒速输注的方式给药;溶剂对照组静脉推注对照液,阳性药对照组静脉给予重组链激酶4 mg·kg-1,三个重组葡激酶组分别静脉给予4 mg·kg-1、2 mg·kg-1、1 mg·kg-1重组葡激酶,静脉推注体积为5 ml,1 min内注毕,输注速度为0.5 ml·min-1,60 min内输毕,120 min后放血处死动物。于给药前及给药后30、60、120 min取静脉血,实验结束后取血栓形成部位的冠脉血管段,分别检测优球蛋白溶解时间(ELT)、血纤维蛋白原含量(Fbg)、纤维蛋白(原)降解产物(FDP)和伤口出血量,检测冠脉血栓溶解率、心肌缺血程度及缺血范围。结果: 与溶剂对照组相比,试验组ELT明显缩短(P<0.05或P<0.01),FDP 明显升高(P<0.05或P<0.01),较少量实验动物Fbg降解超过20%,对小型猪血压及心率无明显影响。与对照组相比,试验组高、中2个剂量组,最大血栓面积分别减少34.3%、15.4%(P<0.05)。与等剂量的重组链激酶相比,重组葡激酶对电刺激引起的冠脉血栓具有更强的溶栓作用(P<0.05或P<0.01),引起的出血副反应少。结论: 重组葡激酶对小型猪冠脉血栓有较好的溶栓作用,相比重组链激酶,溶栓速度快、具有更高的纤维蛋白专一性,出血副反应较少。综合比较, 2 mg·kg-1重组葡激酶具有较好的临床疗效和安全性保障。

关键词: 重组葡激酶, 重组链激酶, 溶栓, 小型猪

Abstract: Objective: To evaluate the thrombolytic effects of recombinant staphylokinase and compare it with those of recombinant streptokinase. Methods: Thirty Chinese experimental miniature pigs were divided into five groups, namely, solvent control group, positive drug control group and three recombinant staphylokinase groups, six in each group. The thrombus of coronary artery was formed by surgical thoracotomy and direct current stimulation in anesthetized animals. Intravenous administration was started after the thrombus of coronary artery was formed for 30 minutes, and the method of first injection and then constant speed infusion by peristaltic pump was used. The solvent control group was injected intravenously with solvent, the positive drug control group was given recombinant streptokinase 4 mg·kg-1 intravenously, and the three recombinant staphylokinase groups were given recombinant staphylokinase at the doses of 4, 2 and 1 mg.kg-1 intravenously. The volume of intravenous injection was 5 ml, which was completed within 1 min, the speed of infusion was 0.5 ml·min-1, which was completed within 60 min, and the animals were sacrificed 120 minutes later. Before and 30, 60 and 120 min after administration, the venous blood samples were collected. At the end of the experiment, the coronary artery segments of the thrombosis site were taken, and the euglobulin dissolution time (ELT), blood fibrinogen content (FBG), fibrinogen degradation product (FDP) and wound bleeding volume were measured respectively. The coronary thrombolysis rate, myocardial ischemia degree and ischemia range were measured.Results: Compared with the solvent control group, ELT in the experimental group was significantly shortened (P<0.05 or P<0.01), FBG degradation in a few experimental animals was more than 20%, FDP was significantly increased (P<0.05 or P<0.01), and there was no significant effect on blood pressure and heart rate of small pigs. Compared with the control group, the maximum thrombus area was decreased by 34.3% and 15.4% (P<0.05) in the high and middle dose groups of the experimental group. Compared with the same dose of recombinant streptokinase, recombinant staphylokinase had stronger thrombolytic effect (P<0.05 or P<0.01) on the coronary thrombus caused by electrical stimulation, less bleeding side effects and the same effect on the degree and range of myocardial infarction as recombinant streptokinase. Conclusion: Compared with recombinant streptokinase, recombinant staphylokinase has faster thrombolysis speed, higher fibrin specificity and less bleeding side effects. In general, 2 mg.kg-1 recombinant staphylokinase has better efficacy and safety.

Key words: recombinant staphylokinase, recombinant streptokinase, thrombolysis, miniature pigs

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