Modeling experiments in animal models of liver cirrhosis
Modeling experiments in animal models of liver cirrhosis
Cirrhosis (hepatic cirrhosis) is a common clinical chronic progressive liver disease with diffuse hepatic damage formed by one or more etiologic factors over a long period of time or repeatedly. Pathohistologically, there are extensive hepatocellular necrosis, nodular regeneration of residual hepatocytes, connective tissue proliferation and fibrous septum formation, leading to destruction of hepatic lobular structure and pseudo lobe formation, and the liver gradually deforms, hardens and develops into cirrhosis. Therefore, the establishment of an animal model of hepatic cirrhosis is of great significance to the study of portal hypertension.
Principle
The basic principle of modeling experiments in animal models of liver cirrhosis is the activation of cytochrome by hepatocytes to generate energy into active trichloromethyl ( CCl3- ) components, trichloromethyl ( CCl3- ) can lead to lipid peroxidation of hepatocyte membranes, which ultimately leads to the destruction of membrane structure. Phenobarbital induces intrahepatic mixed functional oxidase, increases the activity of cytochrome P450, accelerates the conversion of CCl4 to CCl3-, and further aggravates the hepatotoxicity of CCl3-. CCl3- can damage the endoplasmic reticulum of hepatocytes, inducing accumulation of triglycerides and fatty acids, impaired lipoprotein synthesis, and ultimately leading to hepatocellular steatosis. At the same time, CCl3- can damage the mitochondria of hepatocytes, leading to a decrease in the production of reduced coenzyme A (NADH) and adenosine triphosphate (ATP) in the liver, thus inhibiting the tricarboxylic acid cycle and fatty acid oxidation. The repeated action of CCl4, via low concentrations, leads to a process of damage and repair in the liver cell cycle, ultimately leading to the development of liver fibrosis.
Operation method
Modeling experiments in animal models of liver cirrhosis
Principle
The basic principle of modeling experiments in animal models of liver cirrhosis is the activation of cytochrome by hepatocytes to generate energy into active trichloromethyl (CCl3-) components, trichloromethyl (CCl3-) can lead to lipid peroxidation of hepatocyte membranes, which ultimately leads to the destruction of membrane structure. Phenobarbital induces intrahepatic mixed-function oxidase, increases the activity of cytochrome P450, accelerates the conversion of CCl4 to CCl3-, and further aggravates the hepatotoxicity of CCl3-. CCl3- can damage the endoplasmic reticulum of hepatocytes, inducing accumulation of triglycerides and fatty acids, impaired lipoprotein synthesis, and ultimately leading to hepatocyte steatosis. At the same time, CCl3- can damage the mitochondria of hepatocytes, leading to a decrease in the production of reduced coenzyme A (NADH) and adenosine triphosphate (ATP) in the liver, thus inhibiting the tricarboxylic acid cycle and fatty acid oxidation. The repeated action of CCl4, via low concentrations, leads to a process of damage and repair in the liver cell cycle, ultimately leading to the development of liver fibrosis.
Materials and Instruments
Equipment: Move The basic procedure for modeling cirrhosis can be divided into the following steps. A 37 normal grade rabbits weighing 1.75-2.25 kg were used: A 37 common grade rabbits weighing 1.75-2.25 kg were selected, and after 1 week of acclimatization, sodium phenobarbital was injected intraperitoneally once a week at a starting dose of 75 mg/kg once a day for 7 consecutive days. B After that, the dose was 0.1 mL/kg of CCl4 dissolved in salad oil and shaken well at a concentration of 5%. C After the 20th day, depending on the condition of the animals, inject CCl4 twice a week at a dose of 0.14 to 0.26 mL/kg at a concentration of 7% to 13%. D After the 40th day, the dose of CCl4 should be adjusted to 0.36-0.4 mL/kg at 18%-20% concentration according to the diet and body weight of the animals. E After the 60th day, the dose should be adjusted to CCl4, 0.5～0.54 mL/kg, and the concentration should be 25%～27% according to the condition of the animals. For more product details, please visit Aladdin Scientific website.
Syringe, general grade rabbits, etc.
Reagents:
① Phenobarbital sodium.
②CCl
4
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