链脲佐菌素诱导2型糖尿病大鼠年龄和剂量的相关性

Age-and dose-related study of streptozotocin-induced rat model of type 2 diabetes

目的探讨链脲佐菌(STZ)诱导2型糖尿病大鼠模型年龄和剂量的相关性。方法选用清洁级四周龄雄性SD大鼠100只,随机分为饲养4周对照组、4周低剂量组、4周高剂量组、8周对照组、8周低剂量组、8周高剂量组。4周和8周对照组大鼠分别为10只,其余造模组大鼠每组各20只。造模组高脂饲养4周和8周后,用STZ低剂量25 mg/kg和高剂量40 mg/kg腹腔注射进行造模,对照组腹腔注射等量柠檬酸缓冲液。比较注射后第6天各组大鼠成模率和死亡率、肝功、肾功和凝血功能。结果各组大鼠成模率无差异(P>0.05);4周高剂量组死亡率最高,8周低剂量组死亡率最低,死亡率组间有显著性差异(P<0.001);各组造模大鼠血清碱性磷酸酶(AKP)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)值均与其对照组有显著性差异(P<0.05);8周低剂量组血清AKP、ALT、AST值与其他造模组均有组间差异(P<0.05);8周低剂量组血清肌酐(CRE)、尿素氮(BUN)值与对照组无显著性差异(P>0.05),其余各组与对照组均有显著性差异(P<0.05);8周低剂量组与4周低、高剂量组血清CRE、BUN值均有显著性差异(P<0.05);8周低剂量活化部分凝血活酶时间(APTT)与其对照组无显著性差异(P>0.05),其余各组与对照组均有显著性差异(P<0.05);8周低剂量组APTT与其他造模组均有组间显著性差异(P<0.05)。凝血酶原时间(PT)仅4周高剂量组与对照组有显著性差异(P<0.05)。结论8周低剂量组大鼠肝肾功能损伤最小,且无凝血功能障碍,存活率最高。因此,对4周龄大鼠进行8周高脂饲养再以STZ 25mg·kg-1造模是2型糖尿病最佳造模方案。

Objective To explore the correlation between age and drug dose during the modeling of diabetic rats.Methods T 100 clean four week old male SD rats were randomly divided into 4-week-old control group,4-week-old low-dose group,4-week-old high-dose group,8-week-old control group,8-week-old low-dose group and 8-week-old high-dose group.At 4 weeks and 8 weeks,there were 10 rats in the control group and 20 rats in the other model groups.After 4 and 8 weeks of high-fat feeding,STZ low-dose 25 mg/kg and high-dose 40 mg/kg were injected intraperitoneally to establish the model,while the control group was injected with the same amount of citric acid buffer.The modeling rate,mortality,liver function,kidney function and coagulation function of rats in each group on the 6th day after injection were compared.Results There was no significant difference in the modeling rate among the groups(P>0.05),but the mortality of the high-dose group at 4 weeks was the highest,and that of the low-dose group at 8 weeks was the lowest(P<0.001).There were significant differences in serum alkaline phosphatase(AKP),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)between the model group and the control group(P<0.05).The serum AKP,ALT and AST values of low-dose group at 8 weeks were significantly different from those of other models(P<0.05).There was no significant difference in serum creatinine(BUN)and creatinine(BUN)between low dose group and control group(P>0.05).There were significant differences in serum CRE and BUN between 8-week low-dose group and 4-week low-dose and high-dose groups(P<0.05).There was no significant difference in APTT between low dose activated partial thromboplastin group and control group(P>0.05),but there was significant difference between other groups and control group(P<0.05).There were significant differences in APTT between the low-dose group and other models at 8 weeks(P<0.05).The prothrombin time(PT)of high dose group was significantly different from that of normal group(P<0.05).Conclusion The 8 weeks of low dose group showed that the rats had minimal liver and kidney damage after modeling,and coagulation function is not damaged.The 8 weeks of low dose group has the highest survival rate.Therefore,intraperitoneal injection of STZ 25mg/kg after 8 weeks of high-fat feeding is the best model for type 2 diabetes.