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FeCl3诱导的大鼠颈总动脉血栓模型血浆TXA2、PGI2、抗凝和纤溶活性的变化
Changes of TXA2 and PGI2 content and anticoagulative and fibrinolytic activity in the plasma in a rat model of topical FeCl3-induced carotid artery thrombosis
【摘要】 目的探讨FeC l3诱导的大鼠动脉血栓形成模型血浆TXA2、PG I2含量及抗凝、纤溶活性的变化。方法以FeC l3外敷诱导大鼠左侧颈总动脉血栓形成,测定血浆TXA2和PG I2稳定代谢产物TXB2、6-keto-PGF1α含量及t-PA、PAI-1、PLG、AT-Ⅲ和PC活性。结果浓度为2.16 mol.L-1的FeC l3可诱导大鼠颈总动脉闭塞性血栓形成,且该模型血浆TXB2含量升高(P<0.05),6-keto-PGF1α含量降低(P<0.05);血浆t-PA和PLG活性降低(P<0.05),PAI-1活性无变化(P>0.05),t-PA/PAI-1比值降低(P<0.05);血浆AT-Ⅲ活性降低(P<0.01),PC活性轻微降低(0.10>P>0.05)。噻氯匹定可抑制FeC l3诱导的血栓形成,但对TXB2和6-keto-PGF1α无影响,表明其抗栓作用不是通过抑制血小板TXA2生成而实现的;噻氯匹定还可升高血浆t-PA活性,可能系该药通过抑制血栓形成,减少了血浆t-PA消耗所致。而该药对AT-Ⅲ和PC活性无影响。抗凝血药低分子肝素(LMWH)也可抑制血栓形成,该药对TXB2和6-keto-PGF1α无影响。LMWH可升高血浆t-PA活性和t-PA/PAI-1比值,可能与其促进血管内皮细胞释放t-PA有关。LMWH还可使该模型血浆AT-Ⅲ活性降低,这是由于LMWH与AT-Ⅲ结合而发挥其抗凝作用,从而使血浆中AT-Ⅲ消耗所致。结论FeC l3可诱导大鼠闭塞性动脉血栓形成,该模型与血小板活化和凝血系统激活有关,同时该模型存在抗凝蛋白活性降低和纤溶活性降低的病理改变。
【Abstract】 Aim To investigate changes of TXA2 and PGI2 content and anticoagulative and fibrinolytic activity in the plasma in a rat model of topical FeCl3-induced carotid artery thrombosis.Methods Thrombi were induced by topical ferric chloride to left carotid artery in rats.The content of TXB2 and 6-keto-PGF1α(stable metabolite of TXA2 and PGI2, activity of t-PA,PAI-1,PLG,AT-Ⅲ and PC in the plasma in the model of thrombosis were determined.Results Occlusive thrombi were induced by applying FeCl3(2.16 mol·L-1) to left carotid artery.The content of TXB2 was increased markedly(P<0.05),and the content of 6-keto-PGF1α was lower remarkably in the rat plasma(P<0.05).Activities of t-PA,PLG and AT-Ⅲ were lower in the plasma(P<0.05,P<0.01),activity of PAI-1 had no change(P>0.05),but t-PA/PAI-1 ratio reduced(P<0.05).Activity of PC dropped slightly(0.10>P>0.05).Ticlopidine could inhibit thrombosis induced by ferric chloride,but it did not influence TXB2 and 6-keto-PGF1α content and activities of AT-Ⅲ and PC in the plasma.Ticlopidine could enhance activity of t-PA in the plasma.It may be related to the decrease of t-PA consumption by inhibiting thrombosis.Antithrombosis action of ticlopidine may not be concerned to inhibiting production of TXB2 of platelet.LMWH could inhibit thrombosis also,but it did not influence TXB2 and 6-ketoPGF1α content in the plasma.LMWH could enhance activities of t-PA and t-PA/PAI-1 ratio,which may be related to the promoting release of t-PA in vascular endothelial cells.LMWH could reduce activity of AT-Ⅲ,which may be concerned with combination of LMWH and AT-Ⅲ result in AT-Ⅲ consumption.Conclusion Ferric chloride may induce occlusive thrombosis in rats.Thrombosis may be associated with activation of platelet and blood coagulation system,lower of anticoagulative protein and fibrinolytic activity.
【Key words】 thrombosis; model; rat; ferric chloride; thromboxane A2; prostacyclin; fibrinolysis; anticoagulation;
- 【文献出处】 中国药理学通报 ,Chinese Pharmacological Bulletin , 编辑部邮箱 ,2006年11期
- 【分类号】R-332
- 【被引频次】47
- 【下载频次】626