动物造模,药效评价 z-bio 2024-08-22 332

　　(1) Method of replication: Rabbits, regardless of gender, weighing 2-3kg, were sheared, disinfected, and covered with sterile cloth. A 3-4 foot incision was made in the middle of the abdomen under the xiphoid process to expose and separate the common bile duct. A sterile plastic tube with a diameter of 1mm was placed outside the common bile duct, and the tube was ligated with a No. 1 wire and pulled out to cause partial narrowing of the common bile duct. Expose the gallbladder again, insert a needle into the gallbladder body, inject 0.1ml of Escherichia coli solution with a concentration of 1 × 100000/ml, ligate the needle opening, and close the abdominal cavity to complete the modeling surgery. After 15 days, blood was collected from the heart to prepare serum for biochemical testing; Euthanize the rabbit, dissect the liver and gallbladder, extract bile for examination of stone particles or crystals under a low-power microscope, dissect the gallbladder for visual inspection of stone conditions, fix the liver and gallbladder in a 10% formaldehyde solution, and perform histological examination using light microscopy techniques.

　　(2) Model characteristics: Partial narrowing of the common bile duct and injection of Escherichia coli into the gallbladder were performed to create the model. The model rabbits showed signs of mental fatigue, hunched back, loose and dull fur, slow movement, lean appearance, reduced food consumption, scrotal fluid accumulation. Serum biochemical tests showed a decrease in β - endorphin (β - EP), an increase in tumor necrosis factor-a (TNF-a), substance P (SP), γ - glutamyl transpeptidase (γ - GT), alkaline phosphatase (ALP), total bilirubin (TBIL), and conjugated bilirubin (DBIL). Pathological examination shows liver enlargement, multifocal cholestasis, multiple liver abscesses, severe inflammation and liver necrosis, and a large number of liver and bile duct stones; Gallbladder enlargement is more pronounced, with ulceration and necrosis of the cyst wall mucosa, and proliferation of submucosal fibrous tissue. The characteristic of this model is high stone formation rate, with stones appearing in block or sheet form, yellow green or brownish green color, soft and easy to twist, and possibly gallstones or mixed stones. The biggest drawback of this model is its high mortality rate.

　　(3) Comparative medicine shows that human cholecystitis is often caused by bacteria and is often based on bile stasis. This model uses partial narrowing of the common bile duct to cause bile stasis. Changes in the physicochemical properties of bile during stasis can induce the formation of stones in the bile duct, which can stimulate the bile duct, damage the mucosa, and make it easier for injected E. coli to invade, resulting in congestion and edema of the cyst wall mucosa, degeneration, necrosis, and shedding of epithelial cells, and varying degrees of neutrophil infiltration in the wall. Compared to the simple bacterial bile duct infection model, this model is characterized by bile duct stasis, formation of gallstones, and high stone formation rate, which is closer to clinical practice.