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目的:采用烟酰胺(NAA)联合链脲佐菌素(STZ)诱导方法建立2型糖尿病大鼠模型,并探讨NAA的最佳保护剂量。方法:将体重220~250g的雄性wistar大鼠70只随机分为7组,分别为对照组(A组:腹腔注射生理盐水,15min后尾静脉注射柠檬酸缓冲液)和造模组(B-G组:分别先腹腔注射100、120、140、160、180、200mg/kg的NAA溶液,15min后再尾静脉注射65mg/kg新鲜配制的STZ溶液),造模后观察大鼠的尿量及饮水量,每周测定摄食量、体重及空腹血糖(FBG),连续测定4周,实验结束测定各组大鼠糖化血红蛋白(HbA1c)及胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR),同时取大鼠胰腺行病理组织学检查。结果:实验过程只有B组有大鼠死亡,病死率为20%;B~G组的成模率依次为87.5%、80%、40%、20%、0%和0%。与A组相比,造模组中只有B和C组大鼠的饮水量、尿量、摄食量明显增加(P<0.05),体重增长却明显减慢(P<0.05),造模4周只有B和C组的HbA1c、FINS及HOMA-IR与A组比有显著性差异(P<0.05),胰岛细胞数目及体积也显著减少。结论:大鼠腹腔注射120mg/kg NAA,并于15min后尾静脉注射65mg/kg STZ,可制备出成模率高、病死率低、症状明显的2型糖尿病大鼠模型。
OBJECTIVE: To establish a model of type 2 diabetes mellitus in rats by using NAA combined with streptozotocin (STZ) induction and to explore the optimal dose of NAA. Methods: Seventy male Wistar rats weighing 220-250 g were randomly divided into 7 groups: control group (A group: intraperitoneal injection of saline, tail vein injection of citrate buffer after 15 min) and model group (BG group : Respectively by intraperitoneal injection of 100,120,140,160,180,200mg / kg of NAA solution, 15min and then tail vein injection of 65mg / kg of freshly prepared STZ solution), after modeling, the rats were observed urine output and water intake The food intake, body weight and fasting blood glucose (FBG) were determined weekly for 4 weeks. HbA1c and FINS in rats were measured at the end of the experiment. The levels of insulin resistance index (HOMA-IR) At the same time take the rat pancreas pathological examination. Results: In the experiment, only group B rats died, with a mortality rate of 20%. The forming rates of group B ~ G were 87.5%, 80%, 40%, 20%, 0% and 0%, respectively. Compared with group A, the rats in group B and group C only had significantly increased water intake, urine output and food consumption (P <0.05), while the weight gain was significantly slowed down (P <0.05) Only HbA1c, FINS and HOMA-IR in groups B and C were significantly different from those in group A (P <0.05), and the number and volume of islet cells were significantly decreased. CONCLUSION: Rat model of type 2 diabetes mellitus with high morbidity rate, low fatality rate and obvious symptoms can be prepared by intraperitoneal injection of 120mg / kg NAA and intravenous injection of 65mg / kg STZ 15min later.