Antiradiation Effect Of Hydrogen-loaded Nanometer Cerium Oxide Microbubbles On Hematopoietic System In Mice

Background: with the widespread application of nuclear technology,the risk of radioactive damage to the body is greatly increased.There is a lack of a safe,effective,stable and low-toxic anti-radiation drug in clinical practice.Therefore,the development of a new anti-radiation injury drug has a great application prospect.In recent years,studies have shown that both hydrogen and nano cerium oxide have anti-radiation effects,and hydrogen in the form of hydrogen-rich liquid can play an anti-radiation effect by removing reactive oxygen species from the body.Nano cerium oxide is injected into the abdominal cavity in the form of suspension to protect hematopoietic tissues and thus achieve the purpose of radiation resistance.However,the preparation conditions of hydrogen-rich liquid are demanding and storage is difficult,so the application value is not high.Nanometer cerium oxide solution may accumulate in the sternum,duodenum,brain,thymus and lungs,and it has low toxicity,so cerium oxide must enter the body in trace to ensure its safety [5].Ultrasonic microbubbles have been proved to be an ideal carrier,capable ofencapsulating gas and adsorbing fat-soluble substances,with great potential for medical applications.At present,there are few studies on the anti-radiation function of ultrasonic microbubbles.In this study,a safe and stable hydrogen-nanometer cerium oxide microbubble was prepared to investigate its effect on the anti-radiation function of mice.Hydrogen-carrying-nanometer ceria microbubbles can not only improve the application value of hydrogen,but also reduce the dose of nanometer ceria required to reduce the toxic effect of drugs on the body.PART ?: PREPARATION AND CHARACTERIZATION OF HYDROGEN-LOADED NANOMETER CERIUM OXIDE MICROBUBBLESObjective: hydrogen,perfluoropropane,cerium oxide and phospholipid were mixed in a certain proportion to prepare a new type of hydrogen-cerium oxide microbubble.Methods: the nanometer cerium oxide modified by the adsorption of phospholipid membrane material was formed by the inclusion of mixed gas C3F8/H2.Nano cerium oxide modified with 5mg DPPC,2mg mpeg-dppe and 0.5mg titanate was mixed in a tubular bottle,450 ul PBS solution and50 ul glycerin were added,sealed,bathed at 50? for 30 min,cooled to room temperature,and then the mixed gas C3F8/H2 was injected.Silver mercurycapsule mixer horizontal oscillation 50 s,frequency > 4000rpm;Store in refrigerator at 4?.The hydrogen-loaded nanometer cerium oxide microbubbles were characterized and analyzed.After being diluted and centrifuged,the morphology,size and distribution of the microbubbles were observed with a normal microscope.Average particle size was detected by Malvern laser particle size meter.Results: the hydrogen-cerium oxide microbubbles were spherical,with bright center,good dispersibility and no aggregation.The average particle size was(399.1±0.03)nm.Conclusion: after the preparation of hydrogen-loaded nanometer cerium oxide microbubbles by mechanical oscillation method,the particle size distribution was measured to be uniform,and the particle size was small,which was similar to the diameter of red blood cells.PART ? : ANTIRADIATION EFFECT OF HYDROGEN-LOADED NANOMETER CERIUM OXIDE MICROBUBBLES ON HEMATOPOIETIC SYSTEM IN MICEObjective: to study the antiradiation effect of hydrogen-nanometer cerium oxide microbubble on hematopoietic system in mice.Methods: BALB/c mice were randomly divided into two parts,eachpart was randomly divided into a negative control group,a positive control group,and a hydrogen-containing nanometer cerium oxide microbubble group.For each positive control group,the mice in the hydrogen-nanometer ceria microbubble group received 6Gy X-ray irradiation(dose rate 2Gy/min).The natural survival rate of 14 days in three groups of mice was observed.The other three groups of mice were sacrificed on day 3 and day 8 after irradiation,and peripheral blood cell number,spleen and thymus index,bone marrow pathological changes,bone marrow nucleated cell number and spleen histopathological changes were detected.Results: The 14-day survival rates of mice in the positive control group and the hydrogen-cerium oxide microbubble group were 53.3% and73.3%,respectively.On the third day after irradiation,platelets,hemoglobin and erythrocytes in the hydrogen-ceria microvesicle group and the positive control group decreased,but the difference was not statistically significant.There was no significant difference in spleen index between the hydrogen-loaded cerium oxide microbubble group and the positive control group.The WBC count and thymus index of the hydrogen-ceria microbubble group were higher than those of the positive control group(P< 0.05 or P < 0.01).The number of bone marrow cells was reduced in the hydrogen-cerium oxide microvesicle group and the positive control group,which were scattered with cell fragments.The overall structure of thespleen was unclear in the hydrogen-nanometer ceria microbubble group and the positive control group,and the splenic sinus was congested and dilated.Some splenic nodules were observed in the hydrogen-nanometer ceria microbubble group and the positive control group.On the 8th day after irradiation,the erythrocyte number and hemoglobin of the hydrogen-cerium oxide microbubble group and the positive control group decreased,but the difference was not statistically significant.The white blood cell count,platelet and thymus index in the hydrogen-ceria microbubble group were significantly higher than those in the positive control group(P < 0.05 or P < 0.01),and the spleen index was also improved to some extent.There were few bone marrow cells in the positive control group,and there were some bone marrow cells in the hydrogen-ceria microbubble group,but there was apoptosis.In the positive control group,lymphocyte necrosis,depletion,reticulum cell proliferation and megacaryon cell deletion occurred in the spleen of mice.Conclusion: the hydrogen-nanometer cerium oxide microbubble can protect hematopoietic tissue and improve hematopoietic function.