动物造模,心肌病模型 zi-bio 2024-02-18 1132

　　【 Modeling Mechanism 】 Doxorubicin is a commonly used cycle non-specific anti-tumor chemotherapy drug in clinical practice. While anti-tumor, it also forms superoxide free radicals, destroys cell membrane structure and function. Its mechanism of myocardial toxicity is to promote myocardial lipid peroxidation damage, inhibit cardiac sarcoplasmic reticulum enzyme activity, and activate the local myocardium, resulting in increased generation and intracellular calcium overload.

　　【 Modeling Method 】

　　Rabbits: Select 3-month-old Japanese white rabbits with large ears. Dilute doxorubicin with physiological saline injection to 0.5mg/ml, and inject it into the ear vein (1mg/kg) twice a week for a total of 2mg/kg for 8 weeks, with a total dose of 16mg/kg. The control group can receive intravenous injection of physiological saline at the same dose as the experimental group. Ultrasound electrocardiography was used to examine the animals at baseline and 3 weeks after medication completion. The left heart structure and function of the experimental group animals were measured through the anterior chest wall in a non anesthetic state. Both groups of animals were euthanized with 10% potassium chloride three weeks after the last administration, causing cardiac arrest in the diastole phase. The heart was immediately removed, and the free wall myocardial tissue of the left ventricle was taken. It was fixed in 4% paraformaldehyde, embedded in paraffin, sliced, stained, and observed under a light microscope.

　　Rats: Select Wistar rats weighing 210-240g and receive intraperitoneal injection of 2.5mg/kg doxorubicin dissolved in physiological saline, once a week. The normal group was intraperitoneally injected with an equal amount of physiological saline. Adjust the dosage of doxorubicin according to body weight every week. After 6 weeks of medication, stop the medication and observe for 2 weeks. On the 8th weekend, surviving rats and control group rats were anesthetized with chloral hydrate and underwent echocardiography examination. Record the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction, and left ventricular short axis shortening rate of rats. The model rats will have significant differences from the control group. In the 9th week of modeling, rats in the normal group and DCM group were euthanized and their chest cavity was quickly opened to obtain the heart, which was fixed with 10% paraformaldehyde. Cut the heart horizontally with a blade, obtain a cross-sectional view of the heart, measure the left ventricular diameter, and take a photo. Slice the anterior wall myocardium of the left ventricle and stain it with H&E.

　　The method of inducing dilated cardiomyopathy with doxorubicin is widely used due to its convenient sampling, simple method, and satisfactory results. After successful modeling, the left ventricular end diastolic diameter, left ventricular end systolic diameter, right atrioventricular pressure, and left ventricular diameter of the model rats were all larger than those of the control group; Myocardial H&E staining shows disordered arrangement of myocardial fibers, myocardial fiber breakage, widening and edema of intercellular spaces, and partial vacuolar degeneration; Myocardial necrosis mainly occurs at the apex of the heart and beneath the epicardium, and lesions are more common around blood vessels. The pathological characteristics of this type of model are similar to those of humans, but there are also drawbacks, such as high animal mortality rate, long model cycle, and currently there is no unified medication standard.

　　【 Model Evaluation and Application 】 The production method of this DCM animal model has a high success rate, a short modeling cycle, reliable results, and can be used as an animal model for basic research. Long term administration of doxorubicin to rabbits can cause DCM similar to that of humans and can lead to low output heart failure. The toxic side effects of doxorubicin are significant and can easily cause liver and kidney damage, bone marrow suppression, and animal death during the modeling process.