动物造模,药效评价,肝硬化 z-bio 2024-08-22 339

　　(1) Adult baboons were fed with Liebert Decarh ethanol liquid feed using the replication method. The feed formula consisted of 18.6% casein, 0.23% L-cysteine, 0.14% DL methionine, 2.3% corn oil, 7.7% olive oil, 0.72% linoleic acid and ethyl linoleate, 70.3% dextrin and maltose sugars (50% of which were replaced by ethanol) for 24 consecutive months. After the modeling is completed, the liver is removed for histological examination.

　　(2) Model characteristics: The liver of the model animals showed fat infiltration, interstitial inflammation, and fibrous changes, and one-third of the animals showed obvious cirrhosis.

　　(3) One of the causes of human liver cirrhosis in comparative medicine is long-term excessive alcohol consumption. Ethanol is absorbed from the gastrointestinal tract and enters the liver, where it is oxidized to acetic acid by the action of ethanol dehydrogenase and microsomal oxidation system. During this process, coenzyme A (NAD) is converted into reduced coenzyme A (NADH). The decrease in NAD/NADH ratio inhibits the tricarboxylic acid cycle in the liver, weakens gluconeogenesis, reduces fatty acid oxidation, and increases synthesis. When the increase in fatty acids and triglycerides exceeds the liver's processing capacity, their accumulation in the liver leads to fat infiltration, interstitial inflammation, and fibrotic changes, which in turn induce cirrhosis. The establishment and successful replication of this model have confirmed that long-term excessive alcohol consumption can indeed induce liver cirrhosis, and suggest that the existence of the above mechanism is a possible pathway leading to the occurrence of liver cirrhosis. This model conforms to the pathological characteristics of human alcoholic liver cirrhosis, but the expensive experimental animals, long replication cycles, and difficult management severely limit the promotion and use of this method. Prior to this, some people believed that ethanol induced cirrhosis could only occur when accompanied by nutritional deficiency and reaching a certain degree, as it was difficult to replicate a rat model of cirrhosis by simply feeding alcohol. Moreover, ethanol itself can increase the body's demand for choline, and choline deficiency can lead to liver cirrhosis. Therefore, the establishment of alcoholic cirrhosis models often adopts a multi factor collaborative approach for replication, such as the combined application of ethanol and CCl4 for modeling. Ethanol can induce P450 activity and increase the hepatotoxicity of CCl4. Under the hepatic steatosis effect of ethanol, the use of CCl4 can accelerate liver cell necrosis, significantly shorten the modeling time, and reduce the dosage of both to reduce drug side effects and animal intolerance. There are reports that using this method for 60 days can cause liver cirrhosis in mice. This method has the characteristics of stable liver cirrhosis, obvious staging, and low animal mortality rate. If high-fat and low protein foods are used to create a model with ethanol and CCl4, cornmeal is used as feed, 20% lard and a small amount of cholesterol are added, and 30% alcohol is used as the only beverage. Every 3 days, 3-5ml/kg body weight of 40% CCl4 oil is injected subcutaneously, and cirrhosis can be formed after 6 weeks. This method is easy to operate, with a high modeling rate (100%) and a low mortality rate (20%). If sodium phenobarbital is used in combination with alcohol and CCl4 to create a model, animals are first given a solution containing sodium phenobarbital instead of drinking water to drink freely for 2 weeks. Then, 50% to 60% CCl4 oil solution is subcutaneously injected, and 10% to 30% ethanol solution is used as their only drinking water. After 9 weeks, the pathological examination shows that the false lobule formation rate is over 90%.