动物造模,肝衰竭模型 z-bio 2022-01-10 869

　　(1) Reproduction method Adult rats were fasted for 12 hours, and D-galactosamine (D-Gal) was injected intraperitoneally with a body weight of 1.2 to 1.8 g/kg. Alternatively, insert an adult dog or large white pig into general anesthesia, insert a catheter into the left external jugular vein (for drug delivery and blood sampling), insert a femoral artery cannula to monitor blood pressure, and receive the upper skull. . Measure the intracranial pressure (ICP), dissolve D-Gal by 5% glucose injection, and then inject it into the blood vessel at a dose of 0.5-1.5 g/kg body weight from the external jugular vein. After the administration, continuously observe the overall condition of the model animals, record the time of death caused by the poisoning, measure physiological indicators such as blood pressure, pulse, body temperature and intracranial pressure during the whole process, and collect blood to collect blood regularly. For routine biochemical tests and measurement of liver and kidney function, the liver, heart, lungs, kidneys and other organs and tissues were collected for pathological examination after the death or death of the model animals.

　　(2) Model characteristics: 12 hours after the administration, the model rats became lethargic, reduced in activity and yellowed urine. After 30 hours, its response to external stimuli weakened and gradually became drowsy. In stages I and II of endotoxemia and hepatic encephalopathy of varying degrees; serum ALT increased significantly 12 hours after administration, then gradually decreased and returned to normal after 14 days; ALT increased; on the other hand, TBIL, BUN and NH3 levels increase, and PT increases. Extended. The GLU level decreases, the plasma main amino acid content increases, and the branched chain amino acid/aromatic amino acid ratio (BCAA/AAA) decreases. The change trend of the main amino acid content of brain tissue is somewhat similar to that of plasma. However, the content of aspartic acid and glutamate decreased; 40 hours after administration, the EEG frequency decreased, the amplitude increased, and typical three-phase wave changes appeared; at 48 hours, a large number of liver cells were necrotic and the plasma was empty. Blistering, liver cords are covered, and central lobular veins are obviously dilated and congested. Seven days later, the liver cells were still necrotic, with inflammatory cell infiltration in the hilar area. Model rats died on the second day, and the survival rate on the 14th day was between 20% and 30%. After 18 hours of administration to model pigs, ALT, AST, ALP, LDH, TBIL, cholic acid (TB), NH3, tumor necrosis factor-a (TNF-a) began to increase, and arterial blood began to increase 18 to 24 hours later , It started to increase. Ketone body ratio (AKBR) and GLU gradually decreased, blood indigo retention rate increased with time, blood pressure was basically stable, but intracranial pressure increased significantly. There are many scattered bleeding spots in the liver, and extensive necrosis of liver cells accompanied by hemorrhage, but some live liver cells are still found in the middle of the liver lobules, and other organs are obviously damaged. The average survival time of 0.75 g/kg recombinant model pigs was 66 hours, and the average survival time of 1.0 g/kg recombinant model pigs was 43 hours. The symptoms of the model dogs after administration were basically the same as those of the model pigs.

　　(3) Comparative Medicine D-Gal is an amino sugar metabolized in the liver through the galactose pathway. It has strong liver-specific toxicity and can cause severe liver cell necrosis. The main mechanism of action is as follows. Uridine diphosphate glucose (UDPG) formed by specifically binding to uridine trihydrouridine phosphate (UTP) to form uridine diphosphate galactosamine phosphate (UDP-Gal) while phosphorylating galactosamine 1-galactosamine phosphate (UDPG) ) Reduced pyrophosphatase lead UTP content and severely reduced UDPG will inhibit the synthesis of nucleic acid, protein and glycogen in liver cells, destroy the integrity of the liver cell membrane system, cause a large influx of calcium, and destroy liver cells. In addition, it may also aggravate liver cell damage by causing endotoxemia, consuming glutathione, activating liver macrophages and releasing TNF-α. D-Gal is used to replicate the acute liver failure model. The most commonly used animals are rats, but dogs and pigs are also used. The former is usually given by intraperitoneal injection of 1.2-2.3 g/kg body weight, and the latter is usually given by intravenous injection of 0.5-1.5 g/kg body weight. The dose of D-Gal is closely related to the nature, extent and survival rate of animal liver damage. The choice of anesthetic and the length of fasting before the experiment will also affect the development of liver toxicity. For example, the anesthetics halothane and D-Gal have toxic and synergistic effects. Fasting for 12 hours before the experiment may increase the liver toxicity of D-Gal. This model has three main advantages. First, the physical signs, physiological and biochemical indicators, and pathological characteristics of model animals are similar to clinical viral liver failure. Secondly, it has a relatively specific toxic effect on liver tissue, but the spleen has only a small amount of congestion or bleeding. Kidney tissue. , Has no obvious impact on other organizations. Third, the model has a high replication success rate, good repeatability, moderate survival time and specific reversibility, making it suitable for treatment research and efficacy evaluation for various experimental purposes. However, due to the high price of D-Gal, its application is limited, especially for model replication of large animals (such as dogs and pigs), and it requires high doses, which makes the experiment too expensive. This may be because the model is more commonly used.