Study On Mechanisms Of Erythroid Differentiation Damaged By Simulated Space Ionizing Radiation And Microgravity And The Protective Effects Of α-Lipoic Acid

Space radiation,microgravity and other environmental factors may lead to serious dysfunction or irreversible damage of astronauts during long-term deep space flight.The study of the effects of ionizing radiation,microgravity and their combined effects on erythroid differentiation and the protective effects of drugs is of great significance for the correct understanding and alleviation of"space anemia".In this study,we studied the effect of ionizing radiation and ground simulated microgravity on erythroid differentiation of K562 cells induced by hemin as a model of erythroid differentiation and the protective effect ofα-lipoic acid.The main research contents are as follows:1.Establishment of erythroid differentiation model of K562 cellsK562 cells were treated with different concentrations of hydroxylurea（HU）and hemin,cell proliferation activity and erythroid differentiation were measured at different times.And the erythroid differentiation of K562 cells induced by 40μM hemin was selected as the model of erythroid differentiation in subsequent experiments.2.Study on the influence mechanism of ionizing radiation and simulated microgravity effect on erythroid differentiationThe effects of radiation(¹²C⁶⁺、X ray),microgravity and their combined effect were studied by using irradiation,simulated microgravity effects and K562 cells induced by hemin as erythroid differentiation models.After treatment with ¹²C⁶⁺irradiation and simulated microgravity effect,the expression of CD235a were down-regulated,apoptosis and necrosis rates were increased,and ROS contents were sigficantly increased,the combined effect of ¹²C⁶⁺irradiation and simulated microgravity was stronger than that of the two alone.After treatment with X ray irradiation and simulated microgravity effect,the positive rates of benzidine staining and the expression of CD235a were down-regulated;the expression of EPOR and GATA-1 genes related to erythroid differentiation were down-regulated;The cell proliferation inhibition,apoptosis and necrosis rates were increased,and the PIK3R2gene expression was down-regulated after irradiation and microgravity combined treatment.The apoptosis and necrosis rates of cells were increased and the erythroid differentiation rates was decreased after addition of the PI3K inhibitor 3-MA.The results showed that X ray irradiation and simulated microgravity effect had synergistic inhibitory effects on erythroid differentiation,and the mechanism was related to erythroid related transcription factors EPOR,GATA-1 and growth signaling pathway factor PI3K.3.Protective effects ofα-lipoic acid on erythroid differentiation of K562 cells damaged by ionizing radiation and simulated microgravityUsing amifostin as positive control drug,the protective effects ofα-lipoic acid on damaged erythroid differentiation function was studied by detecting cell proliferation activity,apoptosis and necrosis rates,expression of surface marker protein CD235a and intracellular oxidative stress level.It was found that addα-lipoic acid to cells treated with ¹²C⁶⁺ion irradiation and simulated microgravity,the proliferation activity and erythroid differentiation rates increased;apoptosis rates and ROS contents decreased.The results indicate thatα-lipoic acid has similar protective effect on erythroid differentiation damage caused by ionizing radiation and simulated microgravity effect compared with amifostin.