动物造模,心肌病模型,阿霉素 z-bio 2022-02-06 430

　　[Establishment mechanism] Doxorubicin is a commonly used non-specific anti-tumor chemotherapeutic agent in clinical practice. It has anti-tumor effects and forms superoxide free radicals to control the structure and function of cell membranes. The toxic mechanism to the myocardium promotes myocardial lipid peroxidation damage, inhibits the enzyme activity of myocardial sarcoplasmic reticulum tissue, activates the local myocardium to increase production, and intracellular calcium overload.

　　[Modeling method]

　　Rabbit: Choose a Japanese rabbit with big white ears, 3 months old, dilute doxorubicin to 0.5 mg/ml by injection of saline, and then inject it into the ear vein (1 mg/kg) every week for 2 hours for a total of 2 mg/kg for 8 weeks, the total dose is 16 mg/kg. The control group can be injected with the same dose of saline as the experimental group. In the basal state and 3 weeks after the end of the medication, the animals were examined by echocardiography, and the left heart structure and function of the experimental group were measured through the anterior chest wall under non-anaesthesia. Three weeks after the last administration, the two groups of animals were killed with 10% potassium chloride. The heart stops beating during diastole. The heart was taken out immediately, and the left ventricular free wall myocardial tissue was taken out and fixed at 4%. Paraformaldehyde. After embedding in paraffin, section, stain and observe with an optical microscope. at rats: Wistar rats with a body weight of 210-240g are selected, and 2.5 mg/kg doxorubicin dissolved in saline is injected intraperitoneally once a week. The normal group was injected with the same amount of normal saline intraperitoneally. The dose of doxorubicin was adjusted according to body weight every week, and the drug was stopped for 2 weeks after 6 weeks of treatment. At the end of the 8th week, the surviving and control rats were anesthetized with chloral hydrate, and an echocardiogram was performed. Record the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction and left ventricular short axis shortening rate. The model rats are very different from the control group. At 9 weeks of modeling, rats in the normal and DCM groups were sacrificed, and the thoracic cavity was quickly opened to obtain the heart. The heart is fixed with 10% paraformaldehyde. Cut the heart with a blade, take a cross-section of the heart, measure the diameter of the left ventricle, and then take a picture. The myocardium of the anterior wall of the left ventricle was sliced and stained with H&E. [Model Features] The method of dilated cardiomyopathy caused by adriamycin is widely used because of its convenient material, simple method and satisfactory effect. After successful modeling, the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, right ventricular pressure and left ventricular diameter were all larger than those of the control group; myocardial H&E stained myocardial fibers were arranged randomly. Edema, partial ventricular degeneration, myocardial infarction mainly occurs in the root tip and subepithelial, and the lesions mainly occur around the blood vessels. The pathological characteristics of this type of model are similar to humans, but there are also shortcomings. In other words, animal mortality is high, the model period is long, and there is currently no uniform drug dosage standard.

　　[Model Evaluation and Application] The DCM animal model has a high success rate, a short model period, and reliable results. It can be used as an animal model for basic research. Long-term administration of doxorubicin to rabbits can cause DCM similar to humans and may lead to low-power heart failure. Adriamycin has relatively high toxicity and side effects, is prone to liver and kidney damage, bone marrow suppression, etc., and it is easy to kill animals during the modeling process.