卫生研究

目的采用高脂饲料联合链脲佐菌素(STZ)诱导方法建立糖尿病大鼠模型,探讨模型死亡率和成模率的影响因素。方法 8周龄雄性Wistar大鼠在高脂饲料喂养0周、4周、6周或8周后分别腹腔注射30mg/kg STZ;雄性Wistar大鼠在高脂饲料喂养四周后分别腹腔注射20、30或60 mg/kg STZ建立糖尿病模型,做糖耐量实验及胰岛素耐量实验,并检测血清指标,然后再以罗格列酮作为阳性药物进行验证。结果大鼠在高脂饲料喂养4周后,腹腔注射STZ 30 mg/kg处理后,糖尿病大鼠模型成模率分别为85%和80%,高于20 mg/kg STZ组;死亡率为零,显著低于60 mg/kg STZ组(75%);高脂饲料喂养4周后注射30 mg/kg STZ组死亡率最低,而高脂饲料喂养8周模型组死亡率最高达65%。成模大鼠血清甘油三酯、游离脂肪酸显著升高(P<0.05),空腹血清胰岛素未明显下降,并出现糖耐量异常和胰岛素抵抗;罗格列酮治疗4周后血糖、血清甘油三酯及游离脂肪酸显著降低(P<0.05)。结论高脂饲料喂养时间、STZ剂量及鼠龄是影响糖尿病大鼠模型成模率和死亡率的重要因素。

Objective To explore the influencing factors of establishing diabetes mellitus animal model by the combination of feeding high-fat diet for different periods of time and different dosage of streptozotocin(STZ).Method Eight-week-aged male Wistar rats were injected(ip) with 30mg /kg STZ after high-fat diet being fed for 0,4,6 or 8 weeks respectively,and another 100 male rats were injected(ip) with 20mg /kg,30mg /kg and 60mg / kg STZ respectively after high-fat diet being fed for 4 weeks to establish diabetes mellitus models.Intraperitoneal glucose tolerance test and insulin tolerance test were carried out,and plasma indices were also measured.The type of models was verified by the administration(ip) of rosiglitazone.Results The successful rate of modeling in rats fed with high-fat diet for 4 weeks and received 30mg /kg STZ injection(ip) was the highest(85% & 80%).Their plasma triglyceride and free fatty acid were increased significantly(P < 0.05),but the fasting plasma insulin was not different from the control group,these rats also presented impaired glucose tolerance and insulin resistance.The hyperglycemia and blood lipid disorders of these model rats were recovered by the treatment with rosiglitazone.With increasing age and the duration of high-fat diet,the death rate increased rapidly(50% & 65%).The successful rate of modeling at low dose of STZ(20mg /kg,ip) was only 40%.The highest death rate(75%) was observed in rats treated with high dose of STZ(60mg /kg,ip).Conclusion The duration of high-fat diet,the dosage of STZ and the age of rats were the most important factors for the successful rate and death rate while establishing diabetic animal model by the combination of high-fat diet and STZ.