动物造模,肝性脑病动物模型 z-bio 2021-10-29 973

　　Hepatic encephalopathy (HE) is a brain dysfunction caused by liver failure and/or portal systemic hunting (PSS). The degree of neurological or psychological abnormalities varies. Mild asymptomatic changes become more severe. A person may lose consciousness. HE can be divided into three types: AHF type is HF associated with acute liver failure; YHE type is caused by simple portal vein bypass; CHE type is HF that occurs in patients with chronic liver disease, and patients usually develop liver cirrhosis and The collateral circulation of the established portal system is more abundant. This article summarizes the commonly used IIIHE animal models from the perspective of model construction methods, mechanisms, advantages and disadvantages, and behavioral testing.

　　HE type animal model

　　(1) Non-liver animal model

　　The modeling method can use hepatic angiography or total hepatectomy. The liver anastomosis preserves the integrity of the liver, but transfers blood circulation to the liver (portal vena cava anastomosis) and blocks the liver (ligation of the hepatic artery). During total hepatectomy, the blood circulation of the internal organs is bypassed to remove the liver. The mechanism is to cause liver failure by removing the liver or disrupting blood circulation in the liver. Both liver resection and liver angiogenesis models have stellate foot process swelling. Rats after hepatic vascular resection may develop cerebral edema, increased blood ammonia, increased intracranial pressure, and brain diseases. Patients with acute liver failure (ALF) behave similarly. The high mortality rate of 21 hours does not help to observe the healing effect, thus limiting the application of these models. (2) Drug-induced model 1. Thioamide (TAA)-induced mouse model: Gimmcrmann et al. first established a TAA-induced ALF rat model. Experimental animals used in various literatures, including Sprague Dawlcy (SD) rats, female C69BZ injected intraperitoneally with 300 mg/kg per day, and 6 mice injected with 600 mg/kg intraperitoneally for 2 consecutive days, TAA dose and The dosing time is different. Mice were injected intraperitoneally at 100 mg/kg for 3 days. After TAA is absorbed by the liver, it is metabolized by cytochrome P150 mixed function oxidase in liver cells to TAA sulfur oxide, causing lipid peroxidation and damage to liver cells, becoming the DNA, RNA and protein synthase of liver cells, directly kick in. It can produce toxic effects, induce liver metabolism disorders, and cause liver necrosis. The HF model established by TAA has the advantages of good reproducibility, easy operation, high success rate, and high similarity to human HF. 2. A mouse model induced with carbon tetrachloride: CCl 4 was dissolved in mineral oil at a volume ratio of 1:4, and injected intraperitoneally into BALB/c nude mice at a dose of 2.5 mL/kg. CCl. By activating the metabolism of liver microsomal cytochrome P150, it will generate active free radicals and a series of oxidative active substances, which will undergo peroxidation with liver cell plasma membrane or intracellular membrane lipids, decompose membrane phospholipids, and break down membrane phospholipids to destroy integrity , With permeability, cause increased libido and liver cell necrosis. CCl. The price is cheap, but the survival rate of experimental animals is low (24-hour and 48-hour survival rates are 40% and 10%, respectively).

　　3. D-galactosamine-induced rabbit model: established by dissolving D-UalN in a 500-concentration glucose solution and injecting it into the ears of male New Zealand white rabbits at a dose of 1.25 mmol/kg. Has been completed. In this model, astrocyte damage and inhibition of function are the mechanism of HF. This model can replicate stellate cell edema, but experimental animals are relatively expensive.

　　4. Monkey model induced by lipopolysaccharide and amantadine: 1ug/kg lipopolysaccharide and 0.1mg/kg amantadine were dissolved in 50ml saline and slowly injected into the abdominal cavity of female rhesus monkeys. Lipopolysaccharide and α-Tang stopyrin first caused fatty degeneration of rhesus monkey hepatocytes, and eventually led to massive hepatocyte necrosis and explosive liver failure. The rhesus monkey model has metabolic and physiological characteristics similar to human HF. However, it is expensive, the number of studies so far is small, and there is no comparability. 5. A mouse model induced by ethoxymethane: Male C69B 1/6 rats were injected intraperitoneally with 100 mg/kg of AOM. AOM promotes the up-regulation of chemokine ligand 2 (chcmokincligand2, CCL2). In hepatic encephalopathy, CCL2 is related to the activation of microglia and decreased nerve function. This model is very suitable for the study of acute liver injury and hepatic encephalopathy. Despite its reversibility, reproducibility and therapeutic range, AOM is biologically toxic to humans and is suitable for animal body temperature control, requiring caution.