动物造模,药效评价,骨质疏松 z-bio 2024-08-02 494

　　【 Modeling mechanism 】 Primary osteoporosis includes postmenopausal osteoporosis and senile osteoporosis, mainly characterized by decreased bone mass, degeneration of bone microstructure, decreased bone strength and increased fragility, and susceptibility to fractures. Its pathogenesis is complex, and many factors affect its pathogenesis. Endocrine dysfunction is one of the identified pathogenic factors. The secretion level of estrogen in rats with bilateral ovariectomy (castration model) decreased, and its inhibition of osteoclasts was weakened. The function of osteoclasts was active, and the compensatory function of osteoblasts was enhanced. However, the overall trend was that bone resorption was greater than bone formation, and the bones were in a high transition state. The osteoporosis caused by this model is similar to postmenopausal bone loss in human women.

　　[Modeling Method] Healthy female Sprague Dawley rats aged 3-10 months, weighing 300-400g, were selected and fed routinely for one week in the laboratory. 2% pentobarbital sodium (40mg/kg) intraperitoneal anesthesia, taken in prone or supine position, shaved in the surgical area, and disinfected with iodine and ethanol. There are two surgical approaches: one is the dorsal approach, which involves making a longitudinal incision of about 0.8cm on both sides of the lumbar sacral spiny muscle, approximately 1cm above the top of the iliac crest in rats, opening the retroperitoneum, and removing both ovaries; The second approach is the ventral approach. A midline incision of about 1.5cm is made in the abdomen, and the abdominal cavity is opened to expose the ovaries. After lifting, the pedicle is ligated with silk thread, and then the other ovary is removed. The ovary is a deep pink granular tissue that is often covered by surrounding adipose tissue. During surgery, these tissues need to be removed in order to expose them. The surgical method for the control group was the same as that for the experimental group, but the ovaries were not removed after opening the abdominal cavity. Normal diet after surgery can establish an osteoporosis model within 12 weeks.

　　【 Model Features 】 Successful modeling can be achieved 8-12 weeks after surgery, characterized by a decrease in bone density in the femur and the whole body, an increase in the gap between bone cavities, a decrease in bone cells, an increase in osteoclasts, a decrease in the volume, thickness, and quantity of bone trabeculae, and separation of trabecular bones from each other; The cortical bone of the femur becomes thinner, leading to a progressive decrease in bending strength and increased fragility of the femur and tibia.

　　Model Evaluation and Application: Ovariectomy in rats is a recommended model for studying postmenopausal osteoporosis by the US Food and Drug Administration (FDA) and the World Health Organization (WHO). It accurately simulates the clinical characteristics of hormone deficiency in adult women and their response to hormone replacement therapy. The process of osteoporosis in rat trabecular bone is very beneficial for studying the physiological response of bones. Unmated 6-10-month-old female rats are the best choice for preventive research. Female rats aged 10-11 months have important value in studying bone loss after peak bone mass. If the purpose of the experiment is to study the characteristics of adult bone disease progression, bone loss caused by ovariectomy in 10 month old female rats is the preferred animal model. At this point, it has reached the peak of bone density and has clinical manifestations very similar to adult female osteoporosis. In addition, due to the positive correlation between body weight and bone density, a decrease in estrogen levels can lead to weight gain. The increase in bone density during weight gain can partially offset bone loss caused by estrogen deficiency, so animal weight should be appropriately controlled in experiments.

　　The methods for model detection include serum biochemical marker detection, bone tissue morphometry, and bone density measurement. No fragility fractures occurred in rats, but bone fragility can be accurately evaluated through biomechanical experiments on rat bones. In theory, the more evaluation methods there are for osteoporosis models, the better. However, due to limitations such as economic factors, technological equipment, and the number of experimental animals, it is impossible to measure all indicators. Generally, at least two (or more) technical indicators, including bone density, are selected for comprehensive evaluation in the model.