Study Of Mechanism Of RhBMP-2m On Repairing Of Hematopoietic Injury In Exposed Mice

Platelet Factor 4 (PF4) is a member of C-X-C chemokine family and is an abundant platelet alpha-granule. PF4 belongs to the subgroup of non-ELR CXC chemokines. Chemokines with ELR can stimulate newborn blood vessel development, but PF4 has no such effect. PF4 can inhibit newborn blood vessel production and is a negative regulator of hematopoiesis. It acts as an inhibitor of hematopoiesis, particularly of megakaryocytopoiesis.Bone morphogenetic protein (BMP) is a member of the superfamily of Transforming Growth Factor-β (TGF- β ) . BMP was originally recognized as bone inductive protein in repairing large bone defects, but it was subsequently found to play an important role in the induction of embryo development, activation of neural and hematopoietic tissue differentiation. In addition, BMP is an indispensable factor in hematopoiesis. The damage of hematopoietic system is a great complication in the treatment of tumor. Meanwhile, hematologic diseases have some crucial and harmful effects on hematopoietic system. It has been proved that BMP has a close relationshipwith hematopoietic stem cells and marrow stroma cells.PF4 is a negative regulator of hematopoiesis and can inhibit hematopoietic cell proliferation but this effect is reversible. BMP-2m is a positive regulator of hematopoiesis, which regulates hematopoietic cell proliferation and differentiation. Our previous experiments have showed that they have common protective effects on acute hematopoietic injury caused by ~60Co y-ray or chemical drugs; nevertheless, their mechanisms are completely different. The former has preventive effect while the latter has remedial effect.Research 1 Comparison of the effect of PF4 and rhBMP-2m on hematopoietic damage in mice treated with y-rayAIM: To compare the effect of PF4, rhBMP-2m and PF4+rhBMP-2m on hematopoietic damage in mice exposed to high dose of ~60Co-γ ray and to study the synergism of PF4 and rhBMP-2m. METHODS: Thirty-six BALB/c male mice were divided randomly into 6 groups: normal control, irradiated control, PF4, rhBMP-2m, PF4+rhBMP-2m 1 and PF4+rhBMP-2m 2 groups. All the mice except those in normal control group were exposed to 6.5Gy ~60Co-y ray. The hematopoietic parameters of the mice, including the bone borrow cell number, the spleen colony count and the CFU-GM count, were determined on day 10 after exposure to y ray irradiation. RESULTS: The number of bone marrow cells in PF4 group was remarkably higher than that in rhBMP-2m group(P <0.05 )and other groups(P <0.01). The speen colony count in PF4 and rhBMP-2m groups were significantly higher than that in irradiated control group (P<0.01). The CFU-GM count in PF4+rhBMP-2m 1 group was higher than that in other groups (P<0.01) except in PF4+rhBMP-2m 2 group. The DNA concentration in PF4+rhBMP-2m 2 group was the highest. CONCLUSION: Our study suggests that both PF4 and rhBMP-2m exert protective effects on hematopoietic damage following y ray irradiation, but PF4 and rhBMP-2m have no apparent synergism. PF4+rhBMP-2m 2 group shows better effects than...