[Animal modeling] - Pingyangmycin iodine oil emulsion induced liver fibrosis model

  1. Animal modeling materials: 4-5 month old Japanese large eared white rabbits, regardless of gender, weighing (2.5 ± 0.2) kg; Medication: Pingyangmycin iodine oil emulsion.

  2. Modeling method: All experimental rabbits were fasted 24 hours before surgery and were dehydrated 4 hours before surgery. 0.8ml of Su Mian Xin Injection was injected intramuscularly for anesthesia. The incision on the midline of the abdomen was 8cm long. After entering the abdominal cavity, the small omentum (which was actually a small amount of transparent mesangial tissue in the rabbit) was cut off. The liver was found above the pylorus of the stomach, and obvious hepatic artery pulsation was observed, running towards the liver. During the process, it was seen that it emitted from the gastroduodenal artery and ran towards the pylorus. After successfully puncturing the hepatic artery with a No. 5 half scalp needle, the needle crossed the gastroduodenal artery to inject medication. The sham surgery group was injected with 0.4ml of physiological saline; The model group was injected with a suspension emulsion made of 0.2ml iodine oil, 2.0mg Pingyangmycin, and 0.2ml physiological saline; After injection, remove the needle and press with gelatin sponge for 1 minute to confirm no bleeding, then close the abdomen and suture.

  3. Modeling principle: Pingyangmycin iodine oil emulsion (PLE) has a non-specific inhibitory and destructive effect on vascular endothelial cells, which is called "anti vascular effect". After PLE enters the liver, due to the fact that iodized oil can remain in normal liver tissue for nearly 20 days, Pingyangmycin can be slowly released, causing chronic liver injury.

  4. After one week of modeling, the liver surface of the model group was covered with a white membrane and the liver margin was not sharp enough; After 2 weeks, the liver margin further became blunt; At 4 weeks, the overall view is similar to 2 weeks; At 6 weeks, the edge of the liver becomes further blunt, and the surface of the liver is uneven and uneven; At 10 weeks, a hardened nodule with a diameter of about 1cm can be seen on the surface of the liver, which is hard and has a cutting texture that feels like rubber; At 14 weeks, the overall view is similar to that at 10 weeks. The liver margin of the sham surgery group rabbits is sharp, with a smooth surface and bright color.

  After one week of modeling, HE staining showed watery degeneration and swelling of liver cells, crowded liver cords, congestion of liver sinusoids, and extensive lymphocyte infiltration in the portal area; At 2 weeks, HE staining showed significant watery degeneration of liver cells, with empty and bright cytoplasm. Some liver cells showed eosinophilic changes, hepatic sinus congestion, and a large number of lymphocytes infiltrating the portal area. At 4 weeks, HE staining still showed significant watery degeneration of liver cells, with a large number of lymphocytes infiltrating the portal area, significant proliferation of fibrous tissue, thickening of interlobular septa, and congestion of hepatic sinusoids; After 6 weeks of HE staining, the watery degeneration of hepatocytes was alleviated, and the fibrous tissue in the portal area was massively proliferated and extended to the lobule, forming a trend of segmentation and wrapping. In some liver tissues, the hyperplastic fibrous connective tissue was re segmented and wrapped to form pseudo lobules. Under the 10 week light microscope, the liver tissue showed extensive fibrotic changes, and in some areas, there were large clusters of proliferative fibrous connective tissue without obvious liver cell structure; The changes under the mirror in 14 weeks are similar to those in 10 weeks. The morphology of liver cells in the sham surgery group was normal, with neat arrangement of liver cords and clear lobular structures.

  5. Precautions: Strict aseptic operation should be used during surgery to prevent infection.