动物造模,心脏毒性模型 z-bio 2022-09-05 423

　　Objective To evaluate the modeling effect of different concentrations of doxorubicin-induced cardiotoxicity model in mice based on pathological changes.

　　Methods Thirty-six 8-week-old SPF male C57BL/6J mice were randomly divided into normal saline group (NS group), 3 mg/kg doxorubicin group, 4 mg/kg doxorubicin group, and 5 mg/kg doxorubicin group. kg doxorubicin group, 6 mg/kg doxorubicin group, 7 mg/kg doxorubicin group, 6 animals in each group. By intraperitoneal injection, once every 3 days, a total of 10 times, the state of the mice was observed, the heart weight, body weight, heart-to-weight ratio, heart-tibia ratio, and survival were counted, and apoptosis in the heart tissue was detected. The expression of protein, the degree of myocardial fibrosis, the cross-sectional area of the middle of the heart and the cross-sectional area of a single cardiomyocyte were used to evaluate the doxorubicin-induced chronic cardiotoxicity model in mice.

　　Results The survival of the mice in the whole experimental cycle was counted. There were 6 mice in each administration group of 3-5 mg/kg, and the survival rate was 100%. In the 6 mg/kg administration group, 5 mice survived, and the survival rate was 100%. 83. 3%, 1 mouse survived in the 7 mg/kg administration group, and the survival rate was about 16. 7%. Compared with the NS group, the survival rate of the mice in the administration group showed a downward trend, and was negatively correlated with the doxorubicin administration concentration, while the heart weight, body weight, and heart-to-tibia ratio of the mice decreased in a dose-dependent manner. When the concentration of doxorubicin reached 4 mg/kg, compared with the NS group, the proportion of myocardial cell apoptosis in the model group increased, the area of myocardial fibrosis increased, and it was found that the overall heart was reduced, and the cross-sectional area of myocardial cells was correspondingly reduced. Statistical difference (P<0.05).

　　Conclusion The indicators of cardiac fibrosis, cardiomyocyte apoptosis, atrophy and survival rate in mice deteriorated with the increase of doxorubicin accumulation in vivo. Doxorubicin concentration of 4-6 mg/kg was used to construct mice during modeling. The chronic cardiotoxicity model is more suitable. If the dose exceeds this dose, the mortality of mice will be higher, which is not conducive to the later experiments.