动物造模,慢性心脏毒性模型 z-bio 2022-10-19 347

　　Objective To evaluate the effects of doxorubicin in different concentrations on cardiac toxicity in mice based on pathological changes.

　　Methods Thirty six SPF male C57BL/6J mice aged 8 weeks were randomly divided into normal saline group (NS group), 3 mg/kg doxorubicin group, 4 mg/kg doxorubicin group, 5 mg/kg doxorubicin group, 6 mg/kg doxorubicin group, and 7 mg/kg doxorubicin group with 6 mice in each group. The administration method of intraperitoneal injection was adopted, once every 3 days, 10 times in total. The status of mice was observed, and the heart weight, body weight, heart weight ratio, heart to tibia ratio, and survival of mice were counted. The expression of apoptosis protein in heart tissue, the degree of myocardial fibrosis, the cross-sectional area of the middle segment of the heart and the cross-sectional area of a single myocardial cell were detected to evaluate the mouse model of chronic cardiac toxicity induced by doxorubicin.

　　Results According to the statistics of the survival of mice in the whole experimental cycle, 6 mice in each 3~5 mg/kg treatment group survived with a survival rate of 100%, 5 mice in the 6 mg/kg treatment group survived with a survival rate of 83.3%, and 1 mouse in the 7 mg/kg treatment group survived with a survival rate of 16.7%. Compared with NS group, the survival rate of mice in the treatment group showed a downward trend, and was negatively correlated with the drug concentration of doxorubicin, while the heart weight, body weight and heart tibia ratio of mice decreased in a dose-dependent manner. When the concentration of doxorubicin reached 4 mg/kg, compared with NS group, the percentage of cardiomyocyte apoptosis and the area of myocardial fibrosis in model group mice increased, and it was found that the overall size of the heart decreased, and the cross-sectional area of cardiomyocytes decreased accordingly, with statistical difference (P<0.05).

　　Conclusion The indexes of cardiac fibrosis, myocardial cell apoptosis, atrophy and survival rate in mice worsen with the increase of doxorubicin accumulation in vivo. It is appropriate to use doxorubicin at the concentration of 4-6 mg/kg to establish a chronic cardiac toxicity model in mice. If the dose is higher, the mortality of mice is higher, which is not conducive to later experiments.