[Animal Modeling - Pharmacological Evaluation]- Animal Model of Nutritional Insufficiency Cirrhosis

  (1) Method of replication: Male rats were weaned and fed 8-10g of low protein high-fat feed lacking choline daily for 2-3 months. This feed is composed of casein or soybean as the protein source, supplemented with sucrose, lard, vitamin powder, salt, and a quantitative amount of L-cysteine. During the modeling process, the general activity status of the animals is observed daily, and their body weight is measured weekly. After the modeling is completed, whole blood is extracted to prepare serum, and a portion of liver tissue is weighed to prepare homogenate for biochemical testing. Organs such as liver, spleen, and kidney are harvested and weighed to convert them into organ coefficients, and the liver tissue is subjected to histological examination.

  (2) Model characteristics About 20% of the animals died one month after modeling. At the end of two months, the weight growth of the animals stopped, and ascites retention, bleeding, depilation and other phenomena appeared. The giant examination showed typical liver nodules, splenomegaly, ascites retention, pancreatic enlargement, testicular atrophy and other unique symptoms. Some also showed renal sclerosis. Light microscopy showed that at the beginning of modeling, liver tissue was small nodular fatty liver cirrhosis. With the extension of feeding, massive nodular or lobular cirrhosis appeared.

  (3) Dietary imbalance or deficiency of specific nutrients in comparative medicine can lead to liver cell pathology in animals. Experimental results have shown that long-term feeding of choline deficient foods can induce hepatic steatosis, liver fibrosis, and even cirrhosis in rats. This model uses weaned rats because young rats have a higher demand for choline during their developmental stage, and their sensitivity to damage caused by choline deficiency is naturally stronger than that of adult animals. But in fact, sensitivity to choline deficiency depends on the content of intracellular alkaline oxidase. The human liver does not contain choline oxidase and there is no issue of choline deficiency, so this model is not suitable for studying human related diseases in terms of pathogenesis. However, due to the long replication cycle, complex feed preparation, and high cost, it is now rare to see anyone using this method alone to create the model. In addition, male animals and mice were used in the experiment because male animals are more uniform in the process of transitioning to cirrhosis than female animals. Mixing trace amounts of cysteine into feed has a promoting effect on the development of liver cirrhosis.