动物造模,药效评价,肺水肿 z-bio 2024-08-22 511

　　(1) Method of replication: Adult New Zealand rabbits weighing over 2kg were anesthetized with pentobarbital sodium injected intraperitoneally at a dose of 30mg/kg body weight, and their heads and limbs were fixed supine on the operating table. Neck hair removal, routine disinfection of the surgical area, incision of the skin along the midline of the neck, separation of the trachea, and intubation of the trachea. Inject 1:5000 adrenaline 0.4-0.6mg/kg body weight through the rabbit ear vein, observe the animal's respiration and general condition, and record the respiratory curve through a computer biological signal analysis system. When the breathing curve becomes significantly shallower and faster, it indicates that the rabbit has developed pulmonary edema; At this point, the animal is euthanized and the rabbit lung/body ratio is calculated (normal animal lung/body ratios are all less than 1g/100g). Generally, the lung/body ratio is greater than 1g/100g (this method can reach a maximum of 3g/100g or more). During the modeling process of this method, the pulmonary edema index (i.e. lung/body ratio) is an important parameter for evaluating whether animals have developed pulmonary edema. When weighing, attention must be paid to ligating and cutting open tracheal branches to prevent fluid outflow and affect the determination of pulmonary edema index results.

　　(2) The characteristics of the model were pulmonary edema model replicated with adrenaline. After 30 minutes of modeling, the animals could have progressive dyspnea, cyanosis, pink foam like fluid exudation in the mouth and nose, and wet rales could be heard and gradually increased. Macroscopic observation showed that the lungs of the animals were significantly enlarged and swelled. A large amount of pink foam like liquid was seen in the trachea, and pink foam like liquid overflowed on the lung section. Under a light microscope, extensive congestion is observed in the lung tissue, and a large amount of eosin edematous fluid with exudation of red blood cells can be seen in the alveolar cavity and interstitium. Sometimes, the alveolar cavity in the subpulmonary area can be dilated, presenting as compensatory emphysema. If adrenaline is injected intravenously into rats, an ideal pulmonary edema model can also be obtained, but the symptoms of the rat model appear quickly. In addition to the clinical manifestations similar to rabbits, excitement, muscle tremors with muscle weakness, and even convulsions and fainting can be seen in rats, leading to death from respiratory failure.

　　(3) Comparative medicine pulmonary edema refers to a pathological phenomenon in which fluid from the pulmonary vasculature infiltrates into the interstitial and alveolar spaces of the lungs, leading to an increase in fluid outside the pulmonary vasculature. Due to the extremely rich blood vessels in the lungs, the patients may have acute onset clinically. The patients have dyspnea, cyanosis, cough, and can cough hemorrhagic or pink foam like sputum. The lungs have diffuse moist rales. X-ray diagnosis shows that the two lungs are butterfly shaped and flaky fuzzy shadows. Due to the action of adrenaline on the a and β receptors in animal bodies, myocardial contraction is enhanced, heart rate is increased, myocardial oxygen consumption is increased, blood vessels in the skin, mucous membranes, and internal organs of the body contract, ultimately leading to severe constriction of systemic and pulmonary blood vessels, increased cardiac load, and causing dynamic edema. At the same time, adrenaline can directly act on the endothelial cells of pulmonary capillaries, increase platelet and leukocyte aggregation, release oxygen free radicals, cause increased permeability of vascular endothelium and alveolar epithelium, and also promote the formation of pulmonary edema. Therefore, compared with other methods of replicating pulmonary edema models (animal models of pulmonary edema replicated by intravenous injection of oleic acid 0.08ml/kg body weight or intravenous injection of 10% chloroform 0.1ml/kg body weight), this model is closest to the pulmonary edema observed in clinical patients. This model has the advantages of simple experimental operation, economic feasibility, good reproducibility, small influencing factors, and typical clinical symptoms, making it an ideal animal model.