动物造模,药效评价,早期急性呼吸窘迫综合征 z-bio 2024-07-31 439

　　1. Modeling material animal: New Zealand purebred white rabbit, male or female, weighing (1.75 ± 0.25) kg; Medications: Ketamine, Lipopolysaccharide.

　　2. Modeling method: After anesthesia with 0.5mg/kg ketamine in the ear vein, one side of the internal jugular vein and the other side of the carotid artery were separated, and 3F double lumen catheters were placed respectively. Cardiac output was measured using thermal dilution method, and systemic and pulmonary circulation parameters were continuously measured using an American IVY monitor; Separate the right femoral artery and place a single lumen arterial catheter (used for bloodletting during hemorrhagic shock). After the animal fully awakens, basic parameters are recorded, including blood pressure (BP), central venous pressure (CVP), heart rate (HR), respiratory rate (R), body temperature (T), arterial and venous blood gases [PaO2, partial pressure of venous oxygen (PrO2)], cardiac output (CO), etc. The experimental process is divided into 5 observation periods: basic period: after the model animals have fully awakened; Hemorrhagic shock phase: Acute hemorrhagic shock in animal models is induced by rapid bloodletting from the femoral artery catheter (anticoagulated with heparin at a concentration of 12U/ml at room temperature) to maintain a cardiac output below 40% of baseline for 60 minutes (CO measurement every 15 minutes). If necessary, bloodletting can be continued to maintain this level, and parameters of each group are recorded at 60 minutes of shock; Shock recovery period: The released blood is transfused within 30 minutes, and after stabilizing for another 60 minutes, the parameters of each group are recorded. Intravenous injection of LPS for 2 hours: The modeling animals were then intravenously injected with low-dose lipopolysaccharide (1 μ g/kg) for 30 minutes, and the parameters of each group were recorded every 2 hours; Intravenous injection of LPS for 4 hours: observe continuously for 4 hours after intravenous injection of LPS. If there is a decrease in blood pressure or CO in experimental animals, Ringer's solution can be administered intravenously to maintain it. Animals that cannot be corrected are excluded from the experimental scope.

　　3. The modeling principle applies hemorrhagic shock combined with low-dose lipopolysaccharide (LPS) to simulate acute respiratory distress syndrome.

　　4. Changes after modeling: The modeling animals experienced hemorrhagic shock, and there was no significant physiological response at the beginning of intravenous injection of LPS. However, there was a clear deterioration trend over time, and most animals gradually showed an increase in respiratory rate. After intravenous injection of LPS for 4 hours, PaO2 decreased from (11.17 ± 1.86) kPa to (9.31 ± 2.26) kPa, and Qs/Q1 increased from (1.9 ± 0.5)% to (2.3 ± 1.5)%. The pro-inflammatory cytokine IL-1 β also significantly increased, with a significant difference compared to the control group. Under light microscopy, there were no typical exudative changes observed in ARDS.