| ObjectiveTo objectively evaluate the effects of long-term low-dose ionizing radiation(LDIR)on circulatory system diseases(CSD)of radiation workers and the risks of DIR on different types of CSD as well as the possible dose-effect relationship through the radiation epidemiological investigation on the employees in the nuclear units involved in Party A and Party B in China,so as to provide a scientific basis for formulating the occupational health management policies for radiation workers.We searched for possible biomarkers through transcriptomics and bioinformatics analysis,and verified the role of key markers in ionizing radiation-induced atherosclerosis(AS)through in vivo and in vitro experiments,and verified their feasibility as biomarkers in typical populations,thus providing a theoretical basis for the clinical detection and biological mechanism of ionizing radiation-induced AS.Methods1.Epidemiological study of radiation workers(RWs)CSD:Through meta-analysis,status study,retrospective cohort study and case-control study,the relationship between LDIR and CSD and the influence of current LDIR exposure on CSD were analyzed.2.Study of CXCL10 AS a Biomarker of Radiation-Induced AS:Screening of Potential CXCL10 by RWs Blood Sample.The feasibility of building radiation-HUVEC cell model and an ApoE-/-mouse as model was verified,and the accuracy of blood samples of AS patients screened in the RWs were also verified.A linear correlation model was constructed to verify the dose-dependent relationship of CXCL10 with AS and ionizing radiation(IR).Results1.There is preliminary evidence that exposure to LDIR will increase the death risk of chronic obstructive pulmonary disease,ischemic heart disease(IHD)and other chronic obstructive pulmonary diseases.2.Family history of hypertension and other factors together with IR influence CSD of RWs patients;The CSD risk of RWs was lower than that of the control group.The risk of cerebrovascular disease in the external irradiation group was higher than that in the control group.The risk of cardiovascular and cerebrovascular diseases and myocardial infarction(MI)was higher in the high-dose group than in the control group.3.296,568 RWs units were followed up for two person-years,and 240 people died from CSD.The standardized mortality rate was far lower than the national level in 2017;Each CSD had a lower risk of death compared to the IN WORKS and LSS cohorts,and the CeVD had a higher risk of death than the 15-country cohort results.4.There is no evidence that cumulative dose below 200 mSv will increase the risk of chronic obstructive pulmonary disease,there is no evidence that the cumulative dose above 200 mSv(average 496 mSv)will increase the risk of chronic obstructive pulmonary disease and IHD,and there is no evidence that chronic obstructive pulmonary disease and IHD may have a dose-effect relationship.5.The results of transcriptome sequencing of radiation workers showed that compared with the control group,873 differential genes were found in the exposure group.The hub gene was screened out by the up-regulated gene CXCL 10,which is mainly involved in the inflammatory response,CXCR 3 chemokine receptor binding,angiogenesis and other pathways.Through the detection of blood samples from typical populations,both radiation exposure and suffering from AS caused the increase in serum CXCL 10 protein and mRNA levels,and the increase in suffering from AS by radiation workers was the highest.6.X-ray with different doses has an effect on the proliferation and migration of HUVEC cells,with the cumulative effect of 4.0 Gy being the most obvious;The ability to form tubules decreased with the increase of dose,which was dose dependent.AS related biomarkers VC AM1 and CD62E are consistent with the detected mRNA and protein levels of target gene CXCL 10,and both of them have dose-effect relationship with the increase of dose.7.Continuous low dose radiation can induce AS in mice,and the changes of blood pressure,liver function,blood biochemistry,blood routine,aortic AS plaque,etc.;The levels of CXCL10 mRNA and protein in the samples increased with the increase of dose.In blood samples from the RWs group,both IR exposure and the presence of AS caused increases in serum CXCL10 expression,with the highest increase occurring in the presence of AS in the RWs group.Conclusion1.There was no potential for long-term LDIR to predispose radiation workers to a risk of CSD in this study;Groups with cumulative individual doses above 200 mSv(mean 496 mSv)increased the risk of IHD among radiation workers.In 2017,the risk of CSD death of radiation workers in two units is lower than that of the control group and the national level.Except for CeVD,the death risks of radiation workers from two institutions with CSD were lower than those in international cohort studies of the same type.Male radiation workers are at higher risk of chronic obstructive pulmonary disease and death than female radiation workers.2.Continuous accumulated radiation will decrease endothelial function of HUVEC cells;Continuous low dose rate irradiation can induce AS in ApoE-/-mice,and there is a dose-response relationship.3.CXCL10 can be used as a potential biomarker for ionizing radiation-induced Atherosclerosis.4.In order to reduce the risk of chronic wasting diseases among radiation workers,it is necessary to control eating habits,rest habits and prevent chronic diseases. |
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