动物造模,药效评价,心肌病 z-bio 2024-08-01 550

　　[Modeling mechanism] Injecting high-dose norepinephrine into rabbits increases myocardial load, causes myocardial degeneration and necrosis, leading to the occurrence of DCM and congestive heart failure.

　　【 Modeling Method 】 Japanese large eared white rabbits aged around 6 months, weighing 2.1-2.5kg, male and female. Animals were fixed in rabbit cages without anesthesia. The model group received intravenous infusion of norepinephrine at a dose of 1mg/kg. Norepinephrine was added to 40ml of physiological saline and dripped through the ear vein for 90 minutes. The control group only received intravenous infusion of physiological saline, with the same infusion rate and volume as the model group. Experimental data and specimens were collected after 15 consecutive doses of medication. After the modeling is completed, open the chest and take samples.

　　[Model Characteristics] The Ca2+content of peripheral blood red blood cells in this model animal is significantly higher than that in the control group, while the Mg2+content is significantly lower than that in the control group; The Ca2+content in myocardial tissue was significantly higher than that in the control group, while the Mg2+content was significantly lower than that in the control group. The hearts of the model animals have significantly enlarged, softened, and the color of the myocardium has darkened, and some animals may have pericardial effusion. Under light microscopy, myocardial tissue shows patchy or punctate necrosis, with swollen and ruptured myocardial fibers, partial necrosis and fusion, capillary bleeding, microthrombus formation, vacuolar degeneration of some myocardial cells, enlarged and deeply stained nuclei. Under electron microscopy, it can be seen that mitochondria are significantly swollen, cristae are blurred, myofibrils are disordered, even wrinkled and broken, vacuolization is severe, glycogen granules are significantly reduced, lipid droplets are increased, most of the sarcoplasmic reticulum has dilated changes, nuclear chromatin is condensed, secondary lysosomes are increased, myocardial capillaries are edematous, and there are a large number of fluid vesicles in the cytoplasm. In addition, the model animals were accompanied by significant changes in hemodynamics.

　　The rabbit DCM model induced by norepinephrine has the advantages of simple modeling, short time required, and obvious pathological changes, especially suitable for the study of dilated cardiomyopathy and congestive heart failure caused by catecholamine metabolism disorders.