动物造模,原发性糖尿病,药效评价 z-bio 2024-07-05 1113

　　[Spontaneous model] About 10 strains of Chinese hamster diabetes model animals have been cultivated (such as inbred Chinese hamster cultivated by the Experimental Animal Center of Shanxi Medical University), some of which are severe diabetes with ketosis, some are diabetes without ketosis, or only mild diabetes. Almost 100% of offspring born to parents with ketosis exhibit urine glucose positivity, with 50% of animals exhibiting ketosis. It can be used as a model of type 1 diabetes, and also suitable for the study of pre diabetes. There are 4 recessive equivalent heterotopic genes and multiple modifiers involved in the pathogenesis of diabetes in Chinese hamsters with spontaneous diabetes, so different animal strains of diabetes can be bred according to the disease type of diabetes.

　　[Result analysis] Generally, diabetes hamsters have the following manifestations: both male and female hamsters have positive urine glucose reaction (4+++～++++) at an average age of about 8 months, with a positive rate of 28% ～ 35%. The positive rate of urine glucose in male hamsters is slightly higher, but ketonuria is not detected. The weight of animals after birth, when urine sugar is negative, there is no difference between F10 to F11 and the strains of repeated inbreeding, and there is no accompanying obesity. After a positive urine sugar test, there are obvious symptoms of overeating, drinking, polyuria, and hyperglycemia, and a decrease in glucose tolerance. During the 4-8 months of continuous positive urine glucose, compared to urine glucose negative animals, the insulin levels in their blood are roughly the same.

　　Histopathological examination showed no hypertrophy of pancreatic islets, but degenerative changes such as hypertrophy, degranulation, vacuolar degeneration and glycogen infiltration of B-cell nucleus could be seen. The pathological changes of pancreatic islets were similar to those of diabetes animals without ketosis in the Up john population. The characteristic changes of diabetes can be seen in the glomeruli of diseased animals, that is, the glomerular capillaries dilate, the PAS positive substances in the glomerular mesangium increase significantly, the basement membrane of the glomerular sac is hypertrophic, and sometimes the deposition of PAS positive substances can be seen in the renal tubules. The epithelial cells of renal tubules deposit glycogen like substances, and the basement membrane of renal tubules is thickened. The main changes in the retina are the dilation of capillaries from the inner granular layer to the outer reticular layer, and the deposition of PAS positive substances.

　　After the positive reaction of urine glucose in primary diabetes hamsters lasted for 4 to 8 months, vascular damage occurred. Almost 100% of the kidneys and about 50% of the retinal blood vessels were damaged. Compared with Up john group, it is characterized by early onset and high incidence rate. Chinese hamster diabetes is non obese, and is not accompanied by ketosis. From the damage of kidney and retina, it can be used as a model of human diabetes capillary disease. At the same time, it can also be used as a model for pathological analysis of non obese diabetes.

　　By administering insulin, phenformin, and toluenesulfonylurea, blood sugar levels can be controlled and reproduction can be well carried out. Mitian hamsters reproduce after testing positive for urine glucose. Subcutaneous injection of neutral protamine zinc insulin (NPH) at a daily dose of 80-800U/kg can control blood sugar levels. It is very difficult to cultivate and maintain Chinese hamster diabetes strains. Mita switched to feeding lactating infants with monosodium glutamate (MSG), effectively inducing diabetes without obesity. Its histopathology is more than that of diabetes without ketosis