两种实验性糖尿病模型小鼠的比较

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 12 h STZ(45 mg/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 8.0 mmol/L 的为STZ模型鼠。将STZ模型鼠和8周龄空腹血糖大于 8.0 mmol/L 的db/db模型鼠各随机分组,每组8只分别给予罗格列酮(12 mg/kg)、格列苯脲(45 mg/kg)、胰岛素(1 U/kg)和生理盐水(0.1 mL/10 g),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。

Comparison of two kinds of diabetic model mice

AIM: To compare the classical diabetic db/db mice and another diabetic mice which were established by high-fat diet along with STZ injection for evaluating the two diabetic mice on the diabetes characteristic and the reaction to three different kinds of hypoglycemic drug.METHODS: After weaning male BALB/c mice fed with high-fat diet for 4 weeks, streptozocin(STZ)45 mg/kg were intraperitoneal injected once a day and consecutive three days.One week after the last injection, the fasting blood glucose and glucose tolerance were measured. The STZ diabetes mice were prepared successfully as their impaired glucose tolerance accompanying with fasting glucose higher than 8.0 mmol/L. The fasting blood glucose and glucose tolerance of the 8 weeks old db/db mice were also measured.The db/db mice and the STZ diabetes mice were divided into four groups randomly, treated with rosiglitazone(12 mg/kg),glibenclamide (45 mg/kg),insulin (1 U/kg) and normal saline once a day respectively.After four weeks,biochemical indexes and hormone level related to glucose and lipid metabolism were measured from the samples of the two diabetes models.RESULTS: Compared with the BALB/c normal mice, the fasting blood glucose,total cholesterol and triglycerides in STZ model mice were significantly increased(P<0.05) as well as the glucose tolerance was badly impaired, the serum insulin and c-peptide decreased significantly (P<0.05).Compared with the C57BL mice, the fasting blood glucose,total cholesterol,triglyc erides,the serum insulin and the c-peptide lever of db/db mice were all increased significantly (P<0.05)along with the impaired glucose tolerance.In the STZ experiment mice, rosiglitazone, glibenclamide and insulin decrease the fasting blood glucose and improve impaired the glucose tolerance significantly.In the db/db mice, only rosiglitazone can decrease their fasting blood glucose and improve impaired the glucose tolerance, but there was no change after treated with common dose of glibenclamide and insulin until tripling dose of insulin.CONCLUSION: The characteristics of the STZ diabetes mice induced by high-fat diet and multiple low-dose STZ injection were higher achievement ratio, the stable and lasting diabetes characters.The STZ diabetes mice were sensitive to a variety of different hypoglycemic drugs. db/db mice show severe insulin resistance blunting with endogenous and exogenous insulin.db/db mice show only the same sensitive to rosiglitazone as that of the STZ diabetes mice.