[Animal Modeling] - Validation and Regularity Exploration of Establishing a Hyperlipidemia Model with High Fat Diet Feeding

  Objective: To establish hyperlipidemia in SD rats fed with a high-fat diet for 8 weeks, verify the feasibility of the modeling method, and explore the changes in blood lipids of rats at different time points.

  Method: Thirty normal 8-week-old male SD rats were fed adaptively for one week. They were randomly divided into a control group, model group 1, and model group 2 based on body weight, with 10 rats in each group. The control group was given regular feed, while the model group 2 was fed high-fat and high cholesterol feed for 8 weeks. The diet and water of each group were measured daily, and the padding was changed and weighed 4 days later. At the 4th, 6th, and 8th weekends, the animals fasted overnight and collected blood from the orbital venous plexus to measure the four levels of blood lipids in each group. Animals were euthanized over the weekend, and the liver and aorta of each group of rats were collected for HE staining.

  Result: Compared with the control group, the daily average dietary intake of Model 1 group increased, but the difference was not statistically significant; The daily average dietary intake of Model 2 group significantly decreased, and the difference was statistically significant (P<0.01). Compared with the control group, the daily water consumption of the model group and the control group decreased significantly, and the difference was statistically significant (P<0.01). Compared with the control group, the liver/body mass index of the model group and the control group showed significant weight gain, with a statistically significant difference (P<0.01). Compared with the control group, the final weight of Model Group 2 increased, but only Model Group 1 showed statistical significance (P<0.05). In terms of blood lipids, compared with the control group, the TC levels in the 4 and 6 weekend model groups were significantly increased, and the difference was statistically significant (P<0.01 or P<0.05). On the 8 weekend, the LDL-c level in the 1 group of the model group was significantly increased, while the HDL-c level was reduced, and the difference was statistically significant (P<0.05). Liver HE staining showed that the control group had normal arrangement and uniform staining of liver cells, while the model group 2 had extensive steatosis of liver cells, with a few hepatic sinusoids being congested and inflammatory cells infiltrating. Aortic HE staining showed normal aortic structure in three groups.

  Conclusion: The establishment of a high-fat blood model in SD rats fed with high-fat diet resulted in hypercholesterolemia accompanied by severe fatty liver. At the same time, during the experiment of hyperlipidemia in SD rats fed with high-fat and high cholesterol feed, the fluctuation of blood lipids showed a state of elevation, internal adaptation, and elevation. How to overcome the problem of animal anorexia and cholesterol metabolism regulation during the modeling process is the key to feeding high-fat feed into the model.