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目的:通过对链脲佐菌素(STZ)模型鼠和db/db模型鼠的糖尿病模型鼠的特点以及对三类降糖药反应性的比较,客观评价两种糖尿病模型鼠在药物研究中的应用价值。方法:离乳、雄性BALB/c小鼠高脂饲料喂养4周后,空腹12h STZ(45mg/kg)腹腔注射,连续3次,一周后检测糖耐量受损、空腹血糖大于8.0mmol/L的为STZ模型鼠。将STZ模型鼠和8周龄空腹血糖大于8.0mmol/L的db/db模型鼠各随机分组,每组8只分别给予罗格列酮(12mg/kg)、格列苯脲(45mg/kg)、胰岛素(1U/kg)和生理盐水(0.1mL/10g),每天1次,连续给药4周后检测两模型鼠及其对照组糖脂代谢相关的生化指标及激素水平。结果:STZ模型鼠和db/db模型鼠分别与正常BALB/c鼠、C57BL鼠对比,STZ模型鼠和db/db模型鼠均口服葡萄糖耐量试验(OGTT)异常,空腹血糖、血TG和TC显著升高。但STZ模型鼠的胰岛素与C肽水平低于正常;而db/db鼠血C肽、胰岛素浓度显著升高;3种降糖药给药4周后STZ模型鼠的空腹血糖均明显降低,OGTT显著改善;罗格列酮对db/db模型鼠也可显著降低空腹血糖并改善糖耐量,但相同剂量的格列苯脲和胰岛素对db/db模型鼠的空腹血糖和糖耐量无影响。给予3倍剂量的胰岛素,db/db模型鼠才表现出空腹血糖的显著降低。结论:STZ模型鼠胰岛功能受损并有一定程度的胰岛素抵抗,对3种降糖药均敏感。db/db模型鼠表现出高度的胰岛素耐受,对内源性和外源性的胰岛素都不敏感,对罗格列酮的敏感性与STZ模型鼠相当。
OBJECTIVE: To objectively evaluate the effects of two diabetes model mice in drug research by comparing the characteristics of diabetic mice with streptozotocin (STZ) model and db / db model mice and their reactivity to three types of hypoglycemic agents Value. Methods: Male BALB / c mice were fed with high-fat diet for 4 weeks and were injected intraperitoneally with STZ (45mg / kg) twice a day for three times. After one week, the impaired glucose tolerance and fasting blood glucose> 8.0mmol / L For STZ model rats. The rats in STZ model and db / db model rats with 8-week-old fasting blood glucose> 8.0mmol / L were randomly assigned to receive rosiglitazone (12mg / kg), glibenclamide (45mg / kg) , Insulin (1U / kg) and saline (0.1mL / 10g) once a day for 4 weeks. The biochemical parameters and hormone levels related to glucose and lipid metabolism in the two model rats and their control groups were detected. Results: Compared with normal BALB / c mice and C57BL mice, STZ model mice and db / db model mice were both oral glucose tolerance test (OGTT) abnormality, fasting blood glucose, blood TG and TC were significant Rise. But the levels of insulin and C-peptide in STZ model rats were lower than normal; while the blood C-peptide and insulin concentrations in db / db mice were significantly increased; the fasting blood glucose of STZ model rats decreased significantly after 4 kinds of hypoglycemic agents were administered for 4 weeks, But rosiglitazone significantly decreased fasting plasma glucose and glucose tolerance in db / db model rats. However, the same dose of glibenclamide and insulin had no effect on fasting blood glucose and glucose tolerance in db / db model mice. Given a 3 -fold dose of insulin, the db / db model mice showed a significant reduction in fasting plasma glucose. CONCLUSION: The islet function of STZ model mice is impaired and has a certain degree of insulin resistance, which is sensitive to all three hypoglycemic agents. The db / db model mice showed high insulin resistance, insensitivity to endogenous and exogenous insulin, and their sensitivity to rosiglitazone was comparable to STZ model mice.