动物造模,药效评价,急性肺损伤 z-bio 2024-07-25 399

　　1. Animal modeling materials: 24 month old Wistar rats, male or female, weighing (456.5 ± 38.1) g; Medications: oleic acid, lipopolysaccharide O111:B4, ketamine.

　　2. Modeling method: Anesthetize rats by intramuscular injection of 50mg/kg ketamine. Slowly inject 0.175ml/kg oleic acid through the jugular vein, then place the rats back in the cage for free feeding. After 8 hours, slowly inject 2.5mg/kg lipopolysaccharide according to the above method (injection time ≥ 20 minutes). After injection, place the rats in an oxygen chamber and continue to administer oxygen at 1.5L/min for 4 hours. The normal control group (Ns-C) was injected with an equal amount of physiological saline.

　　3. The modeling principle is to establish an elderly acute lung injury (ALI) model by inducing 24 month old Wistar rats with oleic acid and lipopolysaccharides twice.

　　4. Changes after modeling: No systemic inflammatory re response syndrome (SIRS) occurred in the NS-C group, and 64.9% of rats in the modeling group showed systemic inflammatory response, with the standard being: body temperature>ortwice the self control value; Heart rate increased by 50% compared to the self control value; The total number of white blood cells is greater than twice the self control value or less than 50% of the self control value.

　　Pathological changes in lung tissue: The wet dry weight ratio of lung tissue in the model rats was significantly higher than that in the NS-C group, reaching its peak at 6-12 hours after injury. The model shows severe pulmonary congestion, bleeding, and infarction, uneven lung parenchymal density, and often bloody fluid overflow on the cut surface. Under light microscopy, the lesions present as diffuse pulmonary edema, congestion of small blood vessels in the interstitium of the lungs, accumulation of neutrophils in the lumen, formation of microthrombi, and edema around small blood vessels within 1-24 hours after injury. Clear membrane formation, focal infarction, and destruction of alveolar structures can be observed 72-120 hours after injury. Observation by transmission electron microscopy: The model showed severe lesions, significant swelling of pulmonary capillary endothelial cells, abundant fragments of necrotic cells in the alveolar cavity, and significant emptying of cytoplasmic lamellar bodies in type II epithelial cells.

　　In addition to clinical manifestations and pathological examination, PaO2/FiO2<39.99 kPa is the main diagnostic criterion for Au. The incidence of ALI in the modeling group was 59.4% within 1-72 hours after injury. After 120 hours of injury, the PaO2 of the module increased. The mortality rate is 38.3%.