Abstract: BACKGROUND: Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia. In basic studies, models of spleen-deficiency and hyperlipidemia are commonly found in rats, pigs, and other animals. This has limitations for medical research that can only use mouse models. It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia.
OBJECTIVE: To establish a mouse model of spleen-deficiency hyperlipidemia.
METHODS: Totally 24 C57BL/6J mice were randomly divided into normal group (n=12) and spleen-deficiency hyperlipemia group (n=12). Mice in normal group were fed basic diet. Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model. In the first 2 weeks, the mice were forced to swim to their endurance limit on a single day and were only fed cabbage, with free access to water. They were also gavaged with refined lard + high-fat feed on two-day intervals. After 2 weeks, the mice were fed a high-fat diet every day and the diet continued until 12 weeks. The mice were fed with a high-fat diet for 4 and 12 weeks, and their body weight, food intake, gripping strength, fecal water content, small intestinal charcoal propulsion rate, serum D-xylose and gastrin levels, spleen index and thymus index, blood lipid level, total body fat mass, body fat percentage, and liver lipid deposition were tested.  
RESULTS AND CONCLUSION: (1) Compared with the normal group, the body weight, fecal water content, total body fat mass, body fat percentage, triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased (P < 0.05); the daily food intake, gripping force, and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased (P < 0.05); the spleen index of the mice fed with high-fat diet for 4 weeks was increased (P < 0.05); the small intestinal carbon propulsion rate, gastrin level, spleen index, and thymus index of the mice fed with high-fat diet for 12 weeks were decreased (P < 0.05); the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased (P < 0.05). (2) The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group, and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group. (3) The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders, exhaustion, and high-fat feeding. 

Key words: spleen deficiency, hyperlipidemia, mouse, animal model, model evaluation, engineered tissue construction