The Study On Protective Mechanism Of PF4 For ～(60)Coγ Ray Irradiation-induced Bone Marrow Cell Apoptosis In Mice

It has been known for a long time that the bone marrow is one of the most high-sensitive tissues to IR(ionzing radiation) since the early 20th century. As the degree of bone marrow injury is strongly related to the prognosis of patients subjected to IR, great attention has been paid to this area for decades.Current research focus on the mechanism of IR induced hemopoietic injury. It has been documented that not only can IR cause bone marrow cell cell cycle arrest, growth inhibition, but it can induce cell apoptosis. Experiments in vivo and in vitro both confirm that cell apoptosis is the main mode of radiation-induced hemopoietic cell death. The apoptosis of great number of hemopoietic cell plus the depletion of mature blood cell often cause anemia, neutrocytopenia, thrombocytopenia as well as the fatal severe infection and hemorrhage follow with. The decline in the number of residual hemopoietic stem/progenitor cell after IR often render ineffectiveness or unavailability of treatment with GM-CSF or G-CSF. So inhibition of IR-induced bone marrow cell apoptosis is of importance.Platelet factor 4(PF4) is a member of the CXC chemokine family. Initial investigations focused on possible procoagulant roles for PF4, subsequent in vitro studies have, however, described a puzzling array of other apparently unrelated biologic functions, including inhibition of angiogenesis and the proliferation of hemopoietic stem/ progenitor cell, promotion of neutrophil adhesion. So PF4 is called a chemokine enigma.It has been proved by our previous research that PF4 not only can prolong the life time of irradiated mice, increase survival rate and accelerate proliferation of CFU-GM, but also can protect bone marrow hematopoietic function of mice treated by CTX, lessen the cytotoxic effects of CTX on spleen and thymus. These results demonstrate that PF4 has protective effects on hematopoietic system during radiotherapy and chemotherapy. Based on the previous results of our laboratory,we further study the protective effects of PF4 on the bone marrow cells of irradiated mice and initially explore its potential mechanism.AIM: To study the effect of PF4 on murine bone marrow cell apoptosis after irradiation with 5.0Gy ⁶⁰Coγray and explore its potential mechanism. METHODS: 30 male BALB/c mice were randomly divided into three groups: namely normal control group(n=6), PF4 treatmet group(n=12) and irradiation(IR) group(n=12). Mice in PF4 treatmet group were administrated intraperitoneally PF4 40 ug/kg at 26h and 20h respectively before total-body irradiation with 5.0Gy ⁶⁰Coγray. At 4h and 20h after irradiation the apoptosis of bone marrow cells were detected by flow cytometry (FCM).The expression of Bax protein was identified by Western-blot. RESULTS: At 4, 20h after irradiation the apoptotic bone marrow cells in the PF4 group were significantly lower than that in the IR group(p<0.01), the expression of Bax protein in the PF4 group was lower than that in the IR group(p<0.05). CONCLUSION:PF4 can protect bone marrow cells from radiation-induced apoptosis, this is partly due to its down-regulation of proapoptotic protein Bax expression.