动物造模,药效评价,食管静脉曲张 z-bio 2024-08-26 374

　　(1) Method of replication: Adult Beagle dogs were fasted 16 days before surgery and anesthetized with 10mg/kg body weight of ketamine intramuscularly. The animals were then placed on the operating table for fixation. Use pre prepared 8% sodium sulfide for hair removal, connect to an electrocardiogram monitor to monitor changes in the electrocardiogram, and establish an intravenous infusion pathway. Adjust the infusion rate to 60 drops/min. Intravenous injection of propofol and fentanyl, tracheal intubation and connection to a ventilator after muscle relaxation, adjusting tidal volume to 10ml/kg body weight. Intravenous infusion of 80000 U of gentamicin. After hair removal, the skin in the surgical area is routinely disinfected. A surgical knife is used to make a transverse arc-shaped incision of 12-15cm in length on the upper abdomen of the dog, with both ends of the incision reaching the front end of the 11th rib on both sides. After entering the abdomen and exposing and freeing the inferior vena cava and portal vein trunk, an invasive pressure gauge is used to measure the pressure inside the portal vein lumen, and a small tissue biopsy is taken from the liver. After sufficient preparation, perform a bilateral anastomosis of the portal vein and inferior vena cava using a 5-0 vascular line above the level of the right renal vein, with a length of 1.0-2.5cm at the anastomotic site. The main portal vein is anastomosed with the inferior vena cava on one side, and then double ligation of the inferior vena cava above the anastomotic site is performed using a 7-gauge silk thread to completely redirect blood flow from the inferior vena cava system to the portal vein system. Then ligate or suture the main portal vein above the plane of the gastric coronary vein entrance at the hepatic portal, reducing its diameter to 1/3 to 1/2 of its original size. Then, use a 7-gauge silk thread to wrap around the portal vein at the ligation or suture site, with both ends penetrating through the abdominal wall and fixed under the skin with a 1cm long catheter for easy retrieval when tightening the thread after surgery. Before closing the abdominal incision, measure the portal vein system pressure again, check for no active bleeding in the abdominal cavity, good gastrointestinal color and vitality, and then close the abdomen. On the day after surgery, 1000ml of fluid was replenished, 100ml of 0.4% metronidazole injection and 80000 U of gentamicin were intravenously administered. On the second day, stop replenishing fluids and start eating a small amount of food, gradually transitioning to a normal diet; After 2-3 weeks, tighten the silk thread fixed subcutaneously on the abdominal wall to puncture the portal vein, block the portal vein from entering the liver blood flow, and ultimately successfully replicate esophageal varices in dogs. During the model building process, dynamic observation should be conducted through the following methods: preoperative and 6-8 weeks after surgery, abdominal ultrasound gastroscopy examination of esophageal wall thickness and paraesophageal veins; 3-4 weeks after surgery, gastroscopy should be performed once a week to observe the formation of esophageal varices and the presence of portal hypertensive gastrointestinal diseases. The color of the esophageal and gastric mucosa should be observed to determine the presence of portal hypertensive gastrointestinal diseases; 6-8 weeks after surgery, portal vein angiography and vascular imaging video observation were performed.

　　(2) Model characteristics: 1-4 weeks after surgery, the model animals showed a decrease in their appetite and mental state compared to before surgery, poor nutrition, and weight loss. Improvement and recovery began 8-10 weeks later, with weight gain. The intraoperative portal vein pressure measurement showed a significant increase. B-ultrasound examination showed no significant changes in the size and morphology of the liver compared to before surgery, making it difficult to measure and compare the spleen. Partial visible gastric coronary veins with reverse blood flow. No ascites. Compared with preoperative results, the portal vein diameter increased, blood flow velocity increased, and flow rate increased. Preoperative routine gastroscopy and endoscopic ultrasound examination showed smooth esophageal mucosa without varicose veins, and no congestion, edema, or ulcers in the gastric mucosa of the dog. At 6-8 weeks, gastroscopy showed stable size of varicose veins and a 100% formation rate of esophageal veins. Endoscopic micro probe ultrasound revealed thickening of the esophageal mucosal layer, as well as thickening of the paraesophageal and submucosal veins. Through surgical methods, the inferior vena cava blood flow is completely diverted to the portal vein system, and the portal vein blood flow into the liver is blocked in two steps, overcoming the disadvantage of incomplete occlusion of the main portal vein after surgery. The first step is to ligate 1/3 to 1/2 of the main portal vein during surgery. The second step is to tighten the silk thread surrounding the main portal vein 2-3 weeks after surgery, completely blocking the blood flow from the main portal vein into the liver. After 6-8 weeks, a high blood flow and high resistance dog model of esophageal varices with portal hypertension can be created. The postoperative liver and kidney functions of the dog were normal, with no changes in liver tissue structure, no occurrence of hepatic encephalopathy, no esophageal variceal bleeding, and no formation of ascites.