(1) Replication method Male SD rats weighing 230-250g were injected intraperitoneally with CCl4 at a dose of 0.15ml/kg body weight, twice a week, and 0.4g/L phenobarbital solution was used as drinking water for continuous administration The drug was administered for 4 weeks to cause a model of chronic liver damage. At the end of the 4th week, the portal pressure of 1/2 animals was measured. The specific method was as follows: the rats were fasted for 24 hours and then anesthetized, the hepatic triangle was exposed through a median abdominal incision, the portal vein was separated, and the abdominal cavity and abdomen were covered with saline solution during the operation Cotton, insert the 23-gauge needle on the PE-50 catheter into the portal vein to measure the portal vein pressure, and then take the liver for pathological examination. The results of histomorphological examination showed that the rats obviously showed the pathological process of liver cirrhosis after 4 weeks of administration, and the rats showed symptoms of liver cirrhosis after 8 weeks of administration.
Someone also uses carbon tetrachloride (CCl4) plus phenobarbital sodium plus edible liquor to induce. The method is as follows: In the induction period, the experimental animals use a solution containing 0.35 g of phenobarbital sodium per liter of distilled water as the only drinking water for the rats for 1 week. The feed is ordinary rat feed; the modeling period, The 40% CCl4 neutral rapeseed oil solution was intraperitoneally injected at a dose of 0.5ml/100g, twice a week for 4 weeks; at the same time, a 10% ethanol solution (prepared from edible white wine and distilled water) was used as the only drinking water. From the 5th week, it was changed to 50% CCl4 neutral rapeseed oil solution and 0.5ml/100g standard intraperitoneal injection, twice a week, for 4 weeks; at the same time, 30% ethanol solution was used as the only drinking water until the end of the experiment , The preparation time of the rat model of liver cirrhosis and portal hypertension is 9 weeks in total, and the model rate is over 80%.
The standard for modeling is: the portal vein puncture pressure measurement is greater than the control group; the meat heel can observe the formation of cirrhotic nodules and the liver tissue section requires the formation of pseudo lobules. Test indicators include: open abdomen to measure portal venous pressure (PVP) after molding; take blood to test liver function: total serum protein (TSP), albumin (SAB), globulin (SG), total bilirubin (STB), Alanine aminotransferase (OPT), hemoglobin (Hb), platelets (PLT), red blood cells (RBC); liver tissues are sent for pathological section. The model showed extensive formation of false lobules in the liver, re-separation of fibers in the false lobules, and obvious nodules of hepatocyte regeneration.
(2) Features of the model This model has a short production cycle, high mold rate, low mortality, and is suitable for mass production. However, the individual response of rats to CCL varies greatly, which will affect the rate of modeling. It is not as reliable as using dogs as modeling animals.
(3) Compared with medicine, the small animal model also has its advantages. For example, the model is relatively stable and does not require high dietary control. The mechanism of CCl4 inducing chronic liver injury is to directly damage liver cells, destroy various components of cells, and cause fatty degeneration and necrosis of liver cells. Alcohol is an enzyme inducer, which damages mitochondria, increases liver cell oxygen consumption, and can also enhance CCl4 Toxic effects on liver cells, the two simultaneously can promote the formation of liver cirrhosis. Phenobarbital sodium increases the sensitivity of liver cells to CCl4 by increasing the activity of cytochrome P450. Adding phenobarbital sodium to drinking water can promote the development of lasting liver cirrhosis in rats, increase the rate of model formation and reduce animal mortality. The liver cirrhosis model made by this method has histological changes similar to human cirrhosis, and the portal vein pressure is significantly increased and a certain degree of portosystemic tributary shunt occurs.