Experimental Studies Of Fibronectin And Its Recombinant Heparin-binding Domain Polypeptide In The Treatment Of Endotoxemia With Thrombocytopenia In Mice

Fibronectin is known to be a large multifunctional glycoprotein with binding sites for many substances, including heparin, collagen, fibrinogen, fibrin and integrin. It is involved in a variety of cellular processes, such as cell migration, adhesion, hemostasis and tissue repair. And it plays an important role in maintaining the integrity of blood capillary and anti-infection. Many clinical studies suggested that plasma fibronectin concentration might be a prognostic index for endotoxemia. Clinical trails also suggested that reversal of plasma FN deficiency by infusion of FN-rich cryoprecipitate might result in a marked improvement of cardiopulmonary function in the endotoxemia patients. Our previous studies indicated that plasma FN could prevent hepatic failure induced by endotoxin in mice. Recombinant heparin-binding domain of FN is located at its amino-terminal, consisting of 5 typeâ… repeats with 237 amino acids. There had been few reports in the world that the heparin-binding domain in intact FN molecular structure could be used in the treatment of endotoxemia with thrombocytopenia in mice. In the studies, we designed the model of endotoxemia with thrombocytopenia for actual reproduction of the concomitance state of endotoxemia and thrombocytopenia in hematologic disease, and investigate the therapeutical effect of FN and rhFNHN-29 on this state.The subjects of this thesis were focused on the following aspects:1. The construction of the model of endotoxemia with thrombocytopenia in mice...