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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(4): 369-374, 2020 Jul.
Article Zh | MEDLINE | ID: mdl-33167101

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.


Coronary Thrombosis , Metalloendopeptidases , Animals , Coronary Thrombosis/drug therapy , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Metalloendopeptidases/pharmacology , Recombinant Proteins , Swine , Swine, Miniature
2.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(3): 333-7, 2015 Mar.
Article Zh | MEDLINE | ID: mdl-25951640

OBJECTIVE: To explore the effect of Yixintai Granule (YG) on mRNA and protein expression levels of AQP2 in renal medulla of chronic heart failure (CHF) rabbits. METHODS: CHF rat model was established by ear marginal vein injection of adriamycin. Successfully modeled rabbits were divided into the model group, the high (8.4 g/kg), middle (4.2 g/kg), and low dose (2.1 g/kg) YG group, and the Furosemide group (2 mg/kg). Besides, a normal control group was set up. Equal volume of physiological saline was administered to rabbits of the model group and the normal control group by gastrogavage. YG at different doses was administered to rabbits of the 3 YG groups by gastrogavage. The intervention lasted for 4 weeks, once per day. After treatment the urine volume and pathomorphological changes of renal medulla tissue were observed. mRNA and its protein expression levels of AQP2 were detected. RESULTS: Compared with the normal control group, the urine volume decreased significantly, mRNA and protein expression levels of renal medulla AQP2 increased significantly in the model group (all P < 0.01). Compared with the model group, the urine volume increased significantly, and mRNA and protein expression levels of renal medulla AQP2 decreased significantly in all medicated groups (all P < 0.01). Compared with the low dose YG group, the urine volume significantly increased and the mRNA expression level of renal medulla AQP2 significantly decreased in the middle and high dose YG groups (all P < 0.01). The expression level of AQP2 protein significantly decreased in the high dose YG group (P < 0.01). Pathological changes of the renal medulla was the most obviously seen in the model group. But they were alleviated to various degrees in all medicated groups. They were more obviously attenuated in the middle and high dose YG groups. CONCLUSION: YG could improve CHF possibly through down-regulating mRNA and protein expression levels of AQP2 in renal medulla, and elevating the urine volume.


Aquaporin 2/genetics , Drugs, Chinese Herbal/therapeutic use , Heart Failure/drug therapy , Animals , Aquaporin 2/metabolism , Chronic Disease , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Heart Failure/metabolism , RNA, Messenger/metabolism , Rabbits , Rats, Sprague-Dawley
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