促血小板生成素(TPO)的心脏保护作用研究-心胸外科专业论文.docxVIP

The protective effect of thrombopoietin on doxorubicin-induced Cardiomyopathy Major: Cardiovascular Surgery Name: Wei-Zhe, Huang ABSTRACT It was in 1994 that Thrombopoietin（TPO） was purified and cloned as the ligand of c-Mpl. TPO was tranditionally supposed to megakaryocytic linage -specific hematopoietic growth factor through binding to c-Mpl on surface of megakaryocyte since new conception of TPO was raised in 1958. During this decade, TPO was found to exert certain physiological influence on non- hematological tissue, including vascular endothelial cell and ovary, it also have reported that TPO was able to be used as a protective factor against ischemic attack on brain in rat model. However, there was no study that it demonstrated whether TPO have cardiac effect or not. We postulated that TPO have protective effect on damaged heart. Our assumption was logically reasoned by objective result of scientific advance which showed as followed. The mitogenic effect was initiated partly due to combination between TPO and EPO receptor on surfcace of erythoid cell; P13k/Akt was a common pathway shared by anti-apoptotic effect of TPO on HSC and megakaryocyte as well as protective factor on cardiomyocytes; EPO －a corresponding growth factor of TPO, which shared high similarity with TPO as to their structure and gene sequence, prevented cardiomyocytes from apoptosis via P13k/Akt pathway; TPO acted as the third growth factor for hemangioblast and maybe induce formation of capillary vessel in damaged area; bone marrow stem cell which contained mesenchymal stem cells was possibly mobilized by TPO to home in heart and repair the lesion. In our study, damaged cardiac model was induced in vivo as well as in vitro and treated by TPO. Flow cytometry was employed to explore the mechanism of cardiac effect of TPO on heart. Materials and Methods Materials: male BALB/c mouse and H9C2 cell line were kindly provided by Chinese Universitiy of HongKong, rhTPO was brought from PeproTech compa