动物造模,药效评价 z-bio 2024-09-02 387

　　(1) Method of replication: Adult male Wistar rats were fed with conventional standard feed, and their drinking water was changed to 10% ethanol beverage. At the same time, they were orally administered 10ml/kg body weight of 50% ethanol twice a day (with a 12 hour interval) for 14 consecutive weeks. During the modeling period, observe the general activity of the animals. After modeling, euthanize the rats and remove their livers for histological examination.

　　(2) Model characteristics: After administering ethanol to animals, mild cases may walk unsteadily and move stiffly, while severe cases may become intoxicated and drowsy. It takes 30 minutes to 1 hour for the animals to return to normal, and their daily food intake significantly decreases. After continuous oral administration for 14 weeks, the liver volume of the model animals increased, with a dark color and disordered liver cells visible under the microscope. The liver cells swelled and showed balloon like changes, with loose cytoplasm and varying sizes and quantities of fat vacuoles and watery degeneration inside. Multiple punctate or focal necrosis appeared in the lobules, and a large number of inflammatory cells infiltrated the portal area, mainly neutrophils and lymphocytes. Granular or irregular eosinophilic bodies (alcohol bodies) could be seen in the cytoplasm of liver cells. Swelling and proliferation of sinusoidal endothelial cells. Under electron microscopy, it was found that the liver cells of model animals became smaller, with irregular nuclei and uneven expansion of perinuclear spaces. Some liver cell nuclei were sunken, cytoplasm was loose, and the number of organelles was significantly reduced. Mitochondria were swollen and deformed, cristae disappeared, rough endoplasmic reticulum expanded and ruptured, and a large number of lipid droplets and vacuoles of different sizes and filamentous alcohol bodies were visible in the cytoplasm. Lipid storage cells were functionally active.

　　(3) Comparative medicine alcoholic fatty liver refers to a series of clinical syndromes and liver pathological changes characterized by excessive accumulation of fat in liver cells caused by ethanol. Fatty liver or steatosis is the earliest pathological change that occurs in alcoholic liver disease and is the most common liver disease caused by excessive alcohol consumption. The excessive accumulation of fat in the liver is not only due to the deposition of food fat in the liver, but also due to increased fat synthesis under ethanol stimulation, abnormal lipid metabolism leading to free fatty acids, and insufficient degradation or secretion of fat. Therefore, for the preparation of alcoholic fatty liver models on the basis of regular feed feeding, continuous ethanol intake is crucial to maintain high levels of ethanol concentration in the animal's blood, so that its liver can be in a long-term and uninterrupted state of ethanol oxidation metabolism. In this model, rats were continuously given large doses of ethanol once every 12 hours, with 10% ethanol as the sole beverage. After 14 weeks of modeling, hepatic steatosis and alcoholic hepatitis like changes were observed, and some animals also showed reactive proliferation of liver interstitium. These pathological changes were mainly based on increased fat synthesis under ethanol stimulation. The characteristics of this model are that the replication method is simple, the operation is easy, the disease evolution process and pathological features are very similar to those of humans, and the model replication success rate is high.