Study On The Regulation Mechanism Of Platelet Factor 4 To Bone Marrow Cells Cycle Of Acute Radiation Injury Mice

Marrow hematogenic organ is a radiation sensitive tissue. Ionization radiation mainly destroies the proliferation of hematopoitic cells by damaging haemopoietic stem cells or hemopoietic progenitor cells,thus causing disordered cell cycle,especially G1 stage blockage,S stage delay and G2 stage blockage,and finally DNA double-strand break,inducing cell apoptosis. Many researchers thought that G1 stage blockage was an organic protective reaction to the outside stimulation in that it can provide sufficient time to promote the injury DNA repaired before it entered S stage blockage with DNA synthesis and replication. p53 is kernel molecular causing G1 stage blockage. Ionization radiation,as a specific DNA injury factor firstly induced p53 expression,then promoted the downstream WAF1 / CIPl gene , whose protein product,p21 specifically inhibits Cyclin D or Cyclin D/CDK4 synthesis,decreasing expression of Cyclin D,CDK4 as well as loss activity of Cyclin D/CDK4 synthesis , preventing RB protein phosphorylation and E2F releasing,finally let the cells stagnate at G1 stage.Platelet factor 4(PF4) is hemopoiesis negative regulatory factor,synthesized by megacaryocytes. It belongs to CXC family. Previous studies confirmed that PF4 can not only extend the live time of radiation damaging mouse,increasing their survival rates,but also protect the hemopoiesis function of mouse marrow pretreated with CTX,thus alleviating it's injury to thymus and spleen. It has been reported that PF4 can protect the myeloid elements of radiation damaging mouse,mainly through G1 stage blockage,S stage delay and reversible G0/G1 stage blockage into S stage,However,the mechanism of PF4's protective effect is still unknown. The present research based on previous ones,tentatively explored the hemopoiesis protection mechanism of PF4 by detecting G1 stage protein.Objective: To study the protective mechanism of PF4 on the bone marrow cells of acute radiation injury mice by detecting the expression level of p53,Cyclin D1,CDK4. Methods:BALB/c male mice were randomly divided into three groups: control group,exposure group and protection group with PF4. The mice of protection group were injected PF4(40μg/kg) into abdominal cavity twice at 26 h and 20 h before irradiation of 5 Gy 60Co-γray. The expression level of p53,Cyclin D1,CDK4 in BMCs were detected with Western-blotting. Results: Compared with that of control group,the expression of p53 in BMCs of protection group and exposure group was up-regulated,the expression of Cyclin D1,CDK4 in BMCs of protection group and exposure group was down-regelated(P<0.05). The expression of p53 in BMCs of protection group was up-regulated compared with that of exposure group(P<0.05),while the distinction of the expression of Cyclin D1 and CDK4 between protection group and exposure group was not significant,P>0.05.Conclusion: The high expression of p53 may play a key role on the protective mechanism of PF4 for the bone marrow of the radiation injury mice.