| Nuclear attack,nuclear terrorist attack and nuclear accident could produce a large number of acute radiation sickness patients.In order to mitigate the health hazards of nuclear radiation accident and prevent the occurrence of nuclear terrorist attacks,a consensus has become worldwide that we should research a Radiation prevention methods to improve the medical ambulance ability for nuclear and radiation accidents,especially in drug development.Many research institutions have launched a study on the radiation protection of VE compounds.AS a representative of them,United States Armed Forces Radiobiology Research Institute(AFRRI)has been on the international leading level in the field of radiation protection drug research.AFRRI studied three kinds of radiation protection agents,including a-tocopherol succinate(a-TOS),y-tocotrienol(y-T3H)and ?-tocotrienol(?-T3H).However,there are still some problems.One of the problems is the high effective dose(?-TOS:400mg/kg,y-T3H:200mg/kg,?-T3H:300-400mg/kg).The second one is instability of tocotrienol.Therefore,this study explores the hematopoietic protection against irradiation in mice provided by ?-tocopherol and ?-tocopherol succinate.It has reported when a-tocopherol(a-TOH)was esterified into ?-TOS,DRF changed from 1.06 to 1.28.Thus,the first part of the experiment is to explore whether?-TOS has the hematopoietic protection against irradiation in mice which has the same succinic anhydride structure.We evaluate the Effect of ?-TOS on survival rate on 9.2 Gy&9.8 Gy y-ray irradiated mice with a positive control of a-TOS researched by AFRRI.The results showed that ?-TOS or ?-TOS administrated 24hours before irradiation and lhour after irradiation both could significantly improve the survival of 9.2Gy y-ray irradiated mice.When the radiation dose improved to 9.8Gy,?-TOS has a better radiation protection than a-TOS.Also,?-TOS has better radiation protection in a lower administration dosage than other VE compounds reported.Subsequently,by a continuous detection of peripheral blood of mice for 30 days,we found that ?-TOS can significantly improve the number of peripheral blood cells of irradiated mice with a combine of prevention and treatment,as effective as ?-TOS.?-TOS treated after irradiation can promote the recovery of platelets and hemoglobin,but no leukocytes.?-TOS administrated 24hours before irradiation and lhour after irradiation effect better than prevention or treatment administered alone.Finally,we identified the protection of ?-TOS on marrow system by bone marrow nucleated cells(BMNCs)counting and biopsy HE staining of femur and sternum.Bone marrow tissue of mice is depleted at 7 days after irradiation,while?-TOS can significantly improve the number of bone marrow cells and integrity of bone marrow structure.In the second part of the experiment,by granulocyte colony-stimulating factor(G-CSF)screening experiments,it's suggesting that ?-TOH may have some protective effect against irradiation.Firstly,we found ?-TOH do better in early recovery of erythrocyte after irradiation when compared with a-TOS.Then,?-TOH confirmed better protection against irradiation than a-TOS by a 30 days survival experiments after mice irradiated on 8.5Gy y ray.What's more,?-TOH has a lower administration dosage of 1OOmg/kg than a-TOS(400mg/kg).While affirming the protection of ?-TOH against irradiation,a multiple administration of ?-TOH before or after irradiation has begun to research.The results show that multiple administration of ?-TOH before irradiation has no improved effect.The results show that multiple administration of ?-TOH before irradiation has no improved effect.But 3 times administration of ?-TOH after irradiation may improve the recovery of peripheral blood,especially in the late period. |
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