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The Effects on Injured Endothelial Cell by Appling Urokinase at Different Phases after Venous Thrombosis

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Objective Deep Venous Thrombosis (DVT) is the abnormal coagulation of blood in deep venous, and it has become a common disease of vascular surgery. Vascular Endothelial Cell (VEC) locates on the tunica intima and is multifunctinal. It plays important roles on thrombosis, hamostasia, immune, inflammation, vascular growth and the transportion of many materials. VEC expresses heparitin sulfate, antithrombin-III, thrombomodulin, tissue factor pathway inhibitor, tissue-plasminogen activator and plasminogen activator inhibitor to maintain its powerful function of antithrombosis. The injury of endothelial cell is one of the most important factors. When it is damaged by inflammation, hyposia, trauma, et al, venous thrombosis will happen, and the thrombus causes inflammation, hyposia and ischemia in the vessel, which can injur the VEC further. Plenty of reports have verified that urokinase, heparin, tanshinone, et al can protect the form, the stucture and the anticoagulation function of VEC. So VEC is the key aspect in the occurrence, devolepment, treatment and prognosis of DVT. Usually, we choose thrombolytic agent urokinase when treating DVT. It has the ability to activate the plasminogen, and then the fibrin will be degradated by plasmin. At present, the experience of thrombolytic therapy advocates to apply urokinase in the early phase (within 3 days) after DVT, which can obtain more ideal effect and many experiments are taken to support this viewpoint through symptom observation, vein Dopller, phlebography. Actually, only 40 percent of the patients can be treated in time, most of them go to the doctor’s after 3 days. Should we apply normal thrombolytic therapy on them? It is rarely seen to explore the best phases of the treatment of DVT from the study on VEC. We prepare to utilize the rabbit model to observe the effects on injured endothelial cell by administrating urokinase at different phases after venous thrombosis. And we will find the best phase of thrombolytic therapy, which can help us to choose appropriate agents and methods, to lighten the economic burden of the patients. Methods 1 40 Chinese rabbits were randomly divided into 2groups. Group U was the urokinase injection group (n=20). Group M was the model control group (n=20). The DVT model was established by shutting down the bloodcurrent, injuring the vessel wall, injecting thrombin locally. Then definited 5 phases to inject urokinase. They were 12 hours, 24 hours, 72 hours, 7 days, 14 days after the operation, which were represented by A,B, C, D and E respectively. In group U urokinase were applied (15,000u/Kg) once a day to the 4 rabbits, which were randomly selected, and continued for 3 days. There was no therapy put on group M. 2 Animals were killed the day after the therapy ended. The lesioned veins, plasma, were reserved, then the pathological variation, t-PA, PAI activity, the levels of 6-Keto-PGF1α, the amounts of CEC were researched. The data were represented as x ±s , for analysis of test results, we used the SAS system by computer. Results 1 Pathology variation: differences were observed between urokinase group and control group in the phases of A, B and C. In group U,①the shedding of VEC lightened ②the swelling of the remained VEC lessened ③the intimas were more smooth and glossy ④the inflammatory infiltration in the vein walls and the tissues around lightened. While in D and E, there is no significant difference. 2 The variation of antithrombosis function: 2.1 The activities of t-PA and the odds of t-PA/PAI in phases A, B, C of group U were higher than the control group M, and were of statistical significance (P<0.05). When it came to the activity of PAI, there was no statistical significance between the two groups. 2.2 In phases A, B and C of the urokinase group, the levels of 6-Keto-PGF1αin plasma were higher than those in thecontrol group and were statistically significant (P<0.05). 2.3 The amounts of CEC were lower in urokinase group of phases A, B and C than in the control group, and were statis-tically significant (P<0.05).


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