Therapeutic Effect of Fibronectin and Its Recombinant Heparin-Binding Domain Polypeptide on Endotoxemia/Thrombocytopenia in Mice

摘要

We aimed to evaluate the effect of fibronectin (EN) and the recombinant fibronectin heparin-binding domain (rhFNHN-29) polypeptide on endotoxemia in mice with thrombocytopenia in the study. A mouse model of endotoxemia with thrombocytopenia was established and then these mice were injected with FN or rhFNHN-29 polypeptide. Meanwhile, the group of mice received the same volume of saline severed as control group. Sequentially, the mortality rates of mice in all groups were evaluated, hemograms and coagulograms were performed and the serum levels of tumor necrosis factor (TNF)-alpha were measured. Furthermore, the histopathologic features were examined and the expression levels of TNF-alpha, interleukin (IL)-6 and IL-1 beta mRNA were detected in liver tissues of surviving mice in all groups. The results showed that the mortality rate of mice in the saline-treated group was 90%, whereas the mortality rates of mice in the FN- and rhFNHN-29 polypeptide-treated groups were only 20% and 25%, respectively. Compared with saline-treated mice, the hemograms and coagulograms were improved and the plasma TNF-alpha levels were significantly decreased in mice treated with FN or rhFNHN-29 polypeptide. Furthermore, reduced denaturation, necrosis and congestion were found in the livers of mice treated with FN or rhFNHN-29 based on histopathologic analysis. Besides, the levels of TNF-alpha, IL-6 and IL-beta mRNA expression in hepatocytes were significantly decreased in the FN- or rhFNHN-29-treated groups compared with those in the saline-treated group (all P 0.05). Taken together, these results indicated that FN and rhFNHN-29 polypeptide have preventive effects on endotoxemia with thrombocytopenia.