动物造模,药效评价,代谢性白内障 z-bio 2024-08-02 450

　　This type of cataract model forms cataracts by affecting the substance metabolism of the crystalline lens through various drugs, commonly used including D-galactose, sodium selenate, naphthalene, and glucocorticoids, as well as less commonly used drugs such as bleomycin, bleomycin, ibuprofen, cysteamine, and xylazine.

　　1. D-galactose-induced cataract animal model

　　[Modeling mechanism] Excessive D-galactose is metabolized through a bypass pathway in the crystalline lens to form galacturol. Galacturol cannot penetrate the lens capsule and accumulates in large quantities in the crystalline lens, causing an increase in osmotic pressure, swelling and necrosis of lens fibers, and ultimately leading to the formation of cataracts.

　　The modeling method can be divided into three types based on the different ways of lactose intake:

　　(1) High lactose diet: Feeding weaned mice with 50% to 60% lactose can induce cataracts. There are certain differences in the occurrence of different strains, usually H (Holtzman) rats require the shortest time, followed by RW (Rochester colony Wistar) rats, and CN (Carworth Farm Neloon) rats require the longest time. Some people also use guinea pigs instead of rats. Guinea pigs and humans cannot synthesize the daily required vitamin C on their own, and the antioxidant effect of vitamin C can delay the occurrence of cataracts. Therefore, guinea pigs are closer to the formation of human galactosemia induced cataracts. Select 300g of adult guinea pigs and feed them with a diet free of vitamin C and containing 10% lactose, usually for 9 days.

　　(2) Intraperitoneal injection of galactose: Intraperitoneal injection of 50% galactose solution (total amount 15-30g/kg) can cause scattered small vacuoles in the equatorial part of the rat lens 3 days after injection, and by around 17 days, the lens is completely cloudy. If the injection dose is greater than 30g/kg, all test mice will exhibit visible self cataract with completely cloudy crystalline lens, but the mortality rate of the test mice is high; If the dose is less than 15g/kg, the onset of the disease occurs later and the model is unstable.

　　(3) Intraocular injection of galactose: 0.2ml of 0.4% galactose physiological saline was injected into guinea pigs once a day or twice a week for fixed monocular injection. Injecting twice a week results in slow and controllable cataract formation, with clear boundaries between each stage of cataract formation. If injected 0 times a day after the ball, the lens will quickly become completely cloudy.

　　【 Model Characteristics 】 After being given a lactose diet, peripheral vesicles began to appear in the crystalline body on the fourth day and gradually expanded towards the central part; The 7th day is the vesicular phase; On the 10th day, the cortex was significantly cloudy; Typical nuclear opacities begin on the 14th day and are characterized by dense milky white opacities at the center of the lens nucleus; On the 19th day, all remaining animals entered the stage of mature cataracts, with milky white reflections visible in the pupil area and the highest density in the central area. About 30 days after stopping lactose feeding, the reversal begins, and a circular semi transparent area can be seen at the equator with the naked eye. Afterwards, the semi transparent area gradually expands towards the central area and becomes increasingly transparent; After 45 days, the cortical area became almost completely transparent, and slit lamp examination revealed scattered filamentous opacities in the transparent area; After 60 days of examination, only needle sized nuclear opacities remained.

　　In summary, administering galactose to experimental animals through various pathways can induce cataracts. The method of high lactose diet is the simplest, but the results show that it is delayed and the cost is also high. After ball injection, there is less medication and the results are fast, but the operation is complex and there is a significant difference from the physiological state. Intraperitoneal injection not only requires less medication, is easy to operate, and results in faster display, but also approaches a physiological state, making it superior to oral and post balloon injection. However, the disadvantage of intraperitoneal injection of D-galactose is that the mortality rate of the model is relatively high. The reason may be that D-galactose causes high osmotic pressure outside the abdominal tissue, dehydration and sodium removal of organs and tissue cells, organ dysfunction and failure, leading to death. The pathological process of galactose cataract formation is basically the same as that of diabetes cataract, which is mostly used in the study of diabetes cataract.