Form Three-stranded Dna Oligonucleotides To Inhibit Endothelial Cell Tf Expression In Rabbits

Cerebral arterosclerotic thrombosis is one of the most common cerebrovascular disorders. It usually occurs in the narrow,curred and divergent areas of brain blood-vessel,or in valley of arterosclerotic plaque. Cerebral infarction resulted from cerebral arterosclerotic thrombosis is hard to be cured and so to prevent cereral thrombosis has been put an important position. The damage of blood vessel wall,change in blood constituent and aberrance of blood flow are three main factors of thrombosis formation. Many prevention measures were tested to provent the attacks of these abnormal factors. Only about 2O%~?O% inhibitory efficiency of aspirin and ticlopidine on cerebral thrombosis was confirmed by large randomized clinical trials. Furthermore anticoagulants (such as hepariri and warfarin) reduce the 68%棐86% incidence rate of ischemic cerebral vascular disease in patients with heart valvular disease combined with persistent atrial fibrillation. It is suggested that the anticoagulants have an excellent inhibitory action on thrombosis. However these ariticoagulants usually lead to such side effection as severe hemorrhage. Bleeding and clotting time should be determined strictly during the clinical utilization. The inconvenience of the anticoagulants limits their utilization in the prevention of the cerebral thrombosis. Thus, to develop the novel potent anticoagulants without the risk of hemorrhage has become the focus of researches in this field. More recently the role of the tissue factor(TF) has been paied more attention to precoagulation TF, a transmembrane glycoprotein with a molecular mass of 45 kD, is an initiator of the coagulation protease cascade. ?III TF binds factor VII to form the TF-VII compounds that subsequently activates Factor X to Xa, Xa ultimately catalyzes the conversion of prothrombin into thrombin,in turn, fibrin is formed and coagulation of blood initiated. That is the basic process of thrombosis induced by TF. Under the physiological condition a lot of TF is expressed in the tunica adventitia surrounding major blood vessels in important organs, such as brain,lung,kidney,skin, mucosa and so on. This cellular distribution suggests that TF forms a hemostatic envelope that activates the coagulation system promptly when vascular integrity is disrupted. The endothelial cells and monocytes do not express TF under physiological condition. Introvascular coagulation is prevented by physical separation of the coagulation factors in plasma from extravascular cell types that constitutively express TF to guarantee the blood flow easy and smooth. However, in the atherosclerosis the endothelial cells in narrow,curved and divergent brain blood vessels(such as internal carotid artery,basilar artery,middle cerebral artery and so on) express TF owing to long-term sinificant change in local shear stress. Local introvascular thrombosis is rapidly initiated with TF expression in endothelial cells . Shear stress has been proved to be one of the main initiators of thrombosis triggered by TF expression in above-mentioned cerebral blood vessels or valley of plaque of blood vessels. To suppress the expressions of TF in the endothelial cells may be a main step in the prevention of the local introvascular thrombosis. Nevertheless, no research on this hypothesis was found in litrature. The human TF gene is located on chromosome 1 (1 p2 1-22), whose span of cDNA sequence...