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Research On Antithrombotic Effect And Mechanism Of Tetrahydropalmatine

Posted on:2014-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:J YangFull Text:PDF
GTID:2234330398478405Subject:Pharmacology
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Background and ObjectivesTetrahydropalmatine is an alkaloid extracted from the poppy plants Corydalis. Tetrahydropalmatine has long been widely used in clinical practice because of its multiple pharmacological effects such as analgesic, anti-cerebral ischemia, antiarrhythmic and anti-ischemic effect which have been reported. This study focuses on the efficacy and mechanisms of tetrahydropalmatine antithrombotic effectPart1:Research on antithrombotic effect of TetrahydropalmatineMethodsWe further evaluated the antithrombotic effect of tetrahydropalmatne with more pharmacodynamic models. Antithrombotic activity in vivo was determined by causeing rat inferior vena cava ligation. Electrical stimulation induced carotid artery thrombosis model and FeC13induced rat carotid artery thrombosis model. Rabbit non-occlusive venous thrombosis model, arteriovenous shunt model, the PT and APTT and in vivo inhibition of platelet aggregation experiments to evaluate the ability of antithrombotic. Cuticle bleeding model bleeding time.ResultsThe rat inferior vena cava model showed a good antithrombotic effect. Rat electrical stimulation of the model experiments showed that the Tetrahydropalmatine was effective in reducing arterial thrombosis and increasing in carotid arterial blood flow. In the injured rats induced artery endothelial model by FeC13,also significantly inhibited (inhibition rates were8.6%,16.4%and32.8%respectively). And Tetrahydropalmatine can effectively prolong PT and APTT and inhibition of thrombin and ADP induced platelet aggregation.ConclusionTetrahydropalmatine has ovious effect on thrombosisformation and blood coagulation function.Part2:Research on mechanism of TetrahydropalmatineMethodsWe studied the mechanism of Tetrahydropalmatine antithrombotic effect. Vascular endothelial cell apoptosis was determined by immunohistochemical method. And determination of in vitro rat ADP and thrombin-induced tissue factor expression.ResultsApoptosis experiment indicated that tetrahydropalmatine can effectively inhibit the apoptosis after ligation of vessels, but aspirin did not inhibit of apoptosis. PCR results showed that Trimethylpyrazine inhibied tissue factor expression. And Tetrahydropalmatine could effectively reduce the ADP and thrombin-induced tissue factor expression.Conclusion:Tetrahydropalmatine-Antithrombotic effect iseffectively related to the resistance to vascular endothelial apoptosis and inhibition of tissue factor expression.
Keywords/Search Tags:tetrahydropalmatine, thrombosis, platelet aggregation, apoptosis, tissue factor
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