Study On Ferroptosis Of Hematopoietic Progenitor Cells In Bone Marrow Of Irradiated Mice

The main pathological basis of acute radiation sickness of bone marrow type is radiation injury of hematopoietic system of bone marrow.The early stage of radiation injury is visceral hemorrhage caused by the increase of vascular permeability.Red blood cells are the cells with the highest iron content,and visceral hemorrhage is likely to cause local iron accumulation.It has been found that ROS plays an important role in the damage of hematopoietic progenitor cells induced by ionizing radiation.Iron accumulation can induce cell damage through iron mediated lipid peroxidation.The highest form of iron mediated cytotoxicity is iron death,which is a kind of cell death form with iron mediated lipid peroxidation enhancement and glutathione peroxidase 4 inhibition.Based on the above theory,this paper mainly studies the effect of ionizing radiation-induced bone marrow hemorrhage on iron content in bone marrow tissue,and whether there is iron death in radiation-induced bone marrow precursor hematopoietic cell death.Flame atomic absorption spectrometry was used to detect the change of iron content in bone marrow tissue of mice irradiated by γ-ray,and to study the change trend of iron content in bone marrow tissue of irradiated mice;heme oxygenase-1 and hemosiderin-1 were used to study the change mechanism of iron content in bone marrow tissue of irradiated mice;by detecting the iron transporter and iron regulatory protein of bone marrow membrane,serum iron and serum iron regulator,the radiation was studied According to the changes of iron metabolism in the bone marrow of mice,we injected ldn193189,an inhibitor of bone morphogenetic protein receptor,into the abdominal cavity of mice,observed the changes of the number of peripheral blood cells(30 days)and the number of hematopoietic progenitors of granulocyte megaphagocyte system of mice,and studied the damage of iron accumulation on the hematopoietic progenitors of bone marrow;we observed the number of hematopoietic progenitors of granulocyte megaphage system of irradiated mice by the iron death inhibitor The effect of the amount of iron and the detection of the biochemical index of iron death in the bone marrow tissue were studied.The iron death mode of the irradiated mouse bone marrow granulocyte megaphagocyte hematopoietic progenitor cells was studied.Finally,the survival rate of the irradiated mice injected with iron death regulator was observed,and the role of iron death of the bone marrow granulocyte megaphagocyte hematopoietic progenitor cells in the acute radiation sickness of bone marrow type was studied.Results: the results showed that the iron content in bone marrow tissue of mice irradiated with different doses(4 and 8 Gy)increased continuously until 18 days after irradiation.The increase of iron content did not mainly come from the iron element decomposed by heme oxygenase 1,but mainly from hemoglobin iron element(hemosiderin).Irradiation could induce the changes of iron metabolism in bone marrow of mice,which showed that the iron regulatory protein membrane iron transporter axis was activated,while the iron regulatory protein membrane iron transporter axis did not change.Ldn193189 can reduce the iron content of bone marrow tissue by reducing the ferritin of irradiated mice;ldn193189 can significantly alleviate the decrease of the number of granulocyte macrophage hematopoietic progenitor cells induced by irradiation.Iron death inhibitors ferrostat-1 and liproxstat-1can also significantly alleviate the decrease of the number of granulocyte macrophage hematopoietic progenitors induced by irradiation.The content of malondialdehyde and ROS in bone marrow tissue of irradiated mice increased,while the content of glutathione peroxidase 4 decreased.Intraperitoneal injection of ldn193189 or ferrostatin-1 can significantly improve the survival rate of mice irradiated with 10 Gy dose.Conclusion: the hemorrhage induced by γ-ray can induce the accumulation of iron and the corresponding changes of iron metabolism.These changes will eventually lead to the occurrence of iron death of hematopoietic progenitor cells of myelophagocyte,and the iron death of hematopoietic progenitor cells of myelophagocyte plays an important role in the formation of acute radiation sickness.