The Radiation Injury Of Cisplatin Combined With Single High Dose Irradiation On Heart Of Mice

Objective To explore the radiobiological effects of cisplatin combined with single high dose of radiation on heart of mice,so as to provide basic research basis for the heart protection during the process of clinical cisplatin combined with a single high-dose irradiation.Methods A total of 80 male SPF kunming mice were randomized into four groups as A（chemotherapy group）,B（radiotherapy group）,C（chemoradiotherapy group）and D（control group）.The mice in A were given intraperitoneal injection of cisplatin（6mg/kg）on day 1,5,9 and 13;those in B were offered one-time heart irradiation with6MV X-rays at a single high dose of 20 Gy;Those in C received intraperitoneal injection of cisplatin（6mg/kg）on day 1,5,9 and 13 and heart irradiation with 6MV X-rays at a single high dose of 20 Gy in the first day.Those in control group were offered intraperitoneal injection of normal saline and sham irradiation.The first day,we measured the weight of mice and observed the behavior,spirit and feeding status after the experiment,monitor the weight and mental status of mice after the 2nd,4rd,8^th,12^thh and 16^thh week after experiment.The changes of serum cardiac troponin I（cTnI）and myocardial enzyme（AST）spectrum were measured.Hematoxylin-eosin staining was used to observe the changes of heart morphology in mice,and the expression of BCL-2and BAX in heart tissues was detected by immunohistochemistry.Result（1）Compared with the control group,mice in the experimental group began to show weight loss（chemoradiotherapy group was the most obvious）,after 4 week slowly increased of A and C group,while 2 weeks of B group.（2）After irradiation,there were obvious histopathological changes in myocardial tissue in the radiochemical group,with inflammatory reaction,cell edema,vacuolar changes and intercellular arrangement disordered in the early stage,and progressive fibrosis in the later stage.Similar changes occurred in the chemotherapy and radiotherapy groups,but a lesser extent.The myocardial fibers in control group were orderly arranged,the size and morphology of myocardial cells were normal,and the intermyocardial structure was normal.（3）At the same time,the levels of troponin I（cTnI）and aspartate aminotransferase（AST）,in the serum and the expression rates of BCL-2 protein and BAX protein in myocardial tissue were statistically significant(F_cTnI=40.67-105.86,F_AST=19.87-34.84,F_BCL-2=27.31-93.82,F_BAX=68.76-122.45,P<0.01),and pairwise comparison of each indicator at the same time showed that there was no significant difference between group A and group B（P>0.05）,and the differences between other groups were statistically significant（P<0.01）.Conclusion Cardiac injury caused by cisplatin synchronous single high-doseirradiation is more serious than that caused by chemotherapy or radiotherapy alone.Intraperitoneal infusion of cisplatin to a total dose of 24 mg/kg in mice was similar to the degree of cardiac injury induced by single high-dose irradiation,and the mechanism may be related to the increased expression of BAX and the decreased expression of BCL-2.