Cicala Carla, Morello Silvana, Alfieri Alessio, Vellecco Valentina, Marzocco Stefania, Autore Giuseppina
Dipartimento Farmacologia Sperimentale, Università degli Studi di Napoli Federico II, via D. Montesano 49, 80 131 Napoli, Italy.
Eur J Pharmacol. 2007 Dec 22;577(1-3):156-61. doi: 10.1016/j.ejphar.2007.08.007. Epub 2007 Aug 14.
Carrageenan-induced rat paw oedema is a widely used model to investigate the physiopathology of an acute local inflammation. Recently, much attention has been focused on the link between haemostasis and inflammation, and on the impact that inflammation might have on thrombotic events. It is known that the systemic response to inflammation is the "acute phase reaction" that represents a highly complex reaction of the organism to a variety of injuries, aimed to restore homeostasis; one important feature of the acute phase reaction is the hepatic synthesis of proteins involved in the coagulation cascade. Much attention has been focused on the role that systemic inflammation might have on thrombotic events, while there is not much information on the role played by an acute local inflammation on haemostasis, that can lead toward a pro-thrombotic state. The present study was conducted to evaluate the haemostatic balance in the early and the late phase of carrageenan-induced rat paw oedema; i.e. at 3 h, when paw inflammation is maximally expressed, and 24 h following carrageenan injection, when there is an almost complete absence of local inflammatory symptoms. We found that in inflamed animals, 24 h following oedema induction, there was an increase in plasma fibrinogen levels, antithrombin III activity and serum interleukin-6 levels, concomitant to a shortened prothrombin time and to an increased platelet responsiveness to ADP. Furthermore, in inflamed tissues at 3 h there was an increase in antithrombin III proteic expression. Our results demonstrate that a haemostatic imbalance occurs following carrageenan-induced rat paw oedema.
角叉菜胶诱导的大鼠足爪水肿是一种广泛用于研究急性局部炎症生理病理学的模型。最近,止血与炎症之间的联系以及炎症可能对血栓形成事件产生的影响受到了广泛关注。众所周知,机体对炎症的全身性反应是“急性期反应”,它代表了机体对各种损伤的高度复杂反应,旨在恢复体内平衡;急性期反应的一个重要特征是肝脏合成参与凝血级联反应的蛋白质。人们已将大量注意力集中在全身性炎症可能对血栓形成事件产生的作用上,而关于急性局部炎症在止血过程中所起作用的信息却不多,急性局部炎症可能导致血栓前状态。本研究旨在评估角叉菜胶诱导的大鼠足爪水肿早期和晚期的止血平衡,即在注射角叉菜胶3小时(此时足爪炎症表现最为明显)以及注射后24小时(此时几乎完全没有局部炎症症状)进行评估。我们发现,在水肿诱导24小时后的炎症动物中,血浆纤维蛋白原水平、抗凝血酶III活性和血清白细胞介素-6水平均升高,同时凝血酶原时间缩短,血小板对ADP的反应性增强。此外,在3小时时的炎症组织中,抗凝血酶III蛋白表达增加。我们的结果表明,角叉菜胶诱导的大鼠足爪水肿后会出现止血失衡。