The Synergistic Radioprotective Effect Of PGN And WR2721in Rescuing10GY X-ray TBI Mice

Objective To investigate the radioprotective effect of peptidoglycan andamifostine in rescuing10Gy X-ray TBI mice and prolonging their survival time.Methods C57BL/6J mice were randomly divided into PGN+IR,WR2721+IR,PGN+WR2721+IR,IR and normal group. WR2721(150mg/kg) and PGN was admi-nistrated30minutes pre and24hours after irradiation respectively.All groups butnormal group received10Gy(2Gy/min) X-ray total body irradiation(TBI).(1)Recordbody weight and survival rate of all groups in30days.(2)Mice were anesthetiz-ed on days1.25,4,9,16,25,40post IR to assess colitis scoring,to mark crypt stemc-ell in intestine,and to level absorption ability of damaged mice using D-xyloseuptake assay,number of stool in the large intestine.(3)Investigate stem cells’ abil-ity of split and proliferation in bone marrow after radiation and drug administrat-ion with fluorescence-activated cell sorting analysis and clonogenic assays for m-yeloid hematopoietic progenitor colony-forming units.(4)Extract protein of intestinefrom each group to measure amount of TLR2.(5)TLR2-/-mice were randomly d-ivided into PGN+WR2721group,10Gy-exposed group and normal group,and repe-ated above experiments exactly.Results (1)Half of C57BL/6J mice received PGN and WR2721had lived morethan30days,while PGN-and WR2721-alone group died in the9days,and untreatedmice could not live more than5days after IR(p<0.01).(2)Combine treated micerecovery rapidly in40days compare with others.(3)Combine treated mice absorbedmore xylose and retained physiological function in some degree,and colitis score was3.71±0.57,far lower than5.57±1.34untreated group(p<0.05).PGN and WR2721alsowere conducive to protect intestine crypt stem cell.(4)Fluorescence activated cell sortinganalysis showed a small amount of CD34+cells present in all groups,however,micereceived radiation could not formate clone until9days post IR.Combine treated micegradually restored proliferation in a week,after40days the gap between combine and normal mice had not to be identified.But there was no obvious effect on the cytokineswith the two drugs.(5)WR2721seemed not to improve survival rate of mice withoutPGN,comparing TLR2-/-mice given with PGN and WR2721and untreated mice.Conclusion (1)10Gy(2Gy/min) X-ray would damage C57BL/6J and TLR2-/-micehardly,accelerating the mice death.(2)PGN and WR2721synergies on mice,helping withprotection of crypt stem cells and CD34+stem cells,maintaining work of intestine andbone marrow.(3)PGN or WR2721alone treated mice hardly recovery from the acuteradiation sickness.