动物造模,药效评价,急性肺损伤 z-bio 2024-07-23 351

　　1. Modeling material animal: Healthy female New Zealand white rabbit, weighing (3.5 ± 0.4) kg; Drug: Perfluoroisobutylene (PFIB) with a purity of 98%, ethyl carbamate, physiological saline, heparin, potassium permanganate solution; Equipment: Air compression pump, microinjection pump, small animal ventilator, multi-channel physiological recorder.

　　2. Modeling method: After anesthesia with 1mg/kg of 25% ethyl carbamate injected into the ear vein of rabbits, fixation was performed. Routine disinfection and cloth laying were performed, and tracheal intubation was inserted after tracheotomy. Insert a catheter into the right common carotid artery, inject 3mg/kg heparin (1mg=125U) for anticoagulation, and supplement 1mg per hour to monitor arterial pressure and extract blood samples. Insert a catheter into the right external jugular vein to establish a venous channel (5-10 ml/h of physiological saline). The exhaust pipe of the toxic gas mixing chamber (gas flow rate 1L/min) is connected to the inlet of the ventilator (tidal volume 22.2ml/time, frequency 45 times/min), and the outlet of the ventilator is connected to the toxic gas destruction device (potassium permanganate solution). Start the ventilator, adjust the injection speed of the microinjector, and make the PFIB concentration in the gas chamber reach the experimental value (0.3mg/L). Connect the ventilator outlet to a tracheal tube, exhale the gas to the gas destruction device, and mechanically ventilate the rabbit. Close the ventilator at the predetermined time (20-27 minutes) to allow the rabbit to breathe fresh air autonomously.

　　3. Modeling principle: Perfluoroisobutylene (PFIB) is the most toxic cracking product in the production process of various fluorinated polymer compounds (fluoroplastics), with a toxicity about 10 times that of phosgene, which can cause severe lung injury and death.

　　4. Changes after modeling: The PaO2 of the experimental group after 8 hours was (11.31 ± 1.69) kPa, significantly lower than that of the control group (16.19 ± 0.51) kPa. The PaCO2 of arterial blood in the experimental group after 10 hours was (2.33 ± 0.59) kPa, significantly lower than that in the control group (3.66 ± 0.13) kPa.

　　After inhaling PFIB for 10 hours, the blood pressure and heart rhythm of the experimental group decreased. A small amount of white foam like secretion gushed from the endotracheal intubation when the animals in the experimental group were killed.

　　The total protein (0.472 ± 0.061)%, serum protein (0.176 ± 0.060)%, lung wet dry weight ratio (6.87 ± 0.06), and lung capillary permeability coefficient (x 10 ^ -3) (85.7 ± 10.90) of the experimental group were significantly higher than those of the control group [total protein (0.061 ± 0.008)%, serum protein (0.053 ± 0.007)%, lung wet dry weight ratio (4.04 ± 0.25), lung capillary permeability coefficient (x 10 ^ -3) (14.95 ± 1.32)].

　　The lung tissue structure of the control group was normal. The experimental group showed varying degrees of pulmonary edema and pulmonary hemorrhage, alveolar collapse, interstitial congestion and edema, alveolar edema and hemorrhage, and the appearance of a large number of neutrophils and macrophages.

　　5. Precautions: The gender and weight of the experimental animals should be relatively consistent to ensure the consistency of the toxic dose and reduce sampling errors; Strict aseptic operation to avoid interference of infectious factors on experimental results; In order to maintain hemodynamic stability, the speed and quantity of intravenous fluid replacement should be limited to avoid changes in blood indicators caused by human factors and/or high blood volume pulmonary edema; After 10 hours, both the experimental group and the control group showed a decrease in blood pressure and heart rate. To extend the observation time, glucose solution should be supplemented intermittently to ensure heat supply and avoid animal failure; Respiratory management is necessary to maintain airway patency and avoid suffocation caused by blood scabs and secretions blocking tracheal intubation. The amount of heparin added during the experiment should not be too large, as it can ensure smooth arterial catheterization and avoid incision or tracheal mucosal bleeding blocking the tracheal intubation, thereby affecting the animal's lung ventilation function.