【摘要】 目的通过高热量饮食与小剂量多次腹腔注射链脲佐菌素(STZ)的方法建立2型糖尿病小鼠模型。方法采用随机数字表将30只雄性昆明种(KM)小鼠随机分为对照组和模型组(n=15),模型组小鼠饲喂高热量饲料1个月后,连续2~4 d腹腔注射30 mg/kg体重剂量的STZ;对照组则饲喂标准维持鼠料及注射等量柠檬酸盐缓冲液。观测小鼠食水量、体重等一般情况,并于造模后第1、2、4、5、12、21周尾尖采血检测血糖值,在小鼠血糖趋于稳定时检测血清胰岛素(INS),血浆总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL),血浆糖化血红蛋白(Hb A1c)含量,并进行口服葡萄糖耐量试验。结果模型组小鼠存活率为100%。与对照组相比,模型组小鼠注射STZ后体重逐渐下降并于第4周降到最低,此后逐渐回升,直到第21周仍显著低于对照组(t=3.160,P=0.006)。模型组小鼠在造模后血糖水平均明显高于造模前和对照组(P均<0.05);随着时间推移,血糖值也在不断上升,至21周,小鼠血糖值仍旧保持在较高水平的(26.38±1.34)mmol/L。造模后第4周,模型组小鼠的空腹血糖为(11.86±3.33)mmol/L,明显高于对照组的(6.37±1.27)mmol/L(t=-3.830,P=0.002);空腹血清胰岛素水平与对照组差异无统计学意义[(5.73±0.24)m U/L比(5.48±0.32)m U/L;t=-0.863,P=0.416];胰岛素敏感指数为0.0145±0.0039,明显低于对照组的0.0267±0.0039(t=4.414,P=0.003)。造模后第6周,模型组小鼠在口服灌胃葡萄糖0、30、60、120 min后的血糖分别为(15.35±1.82)、(26.45±1.07)、(25.58±1.46)、(26.15±1.00)mmol/L,均明显高于对照组的(6.88±1.75)(t=-8.203,P=0.000)、(17.65±2.94)(t=-6.884,P=0.000)、(13.18±2.04)(t=-12.110,P=0.000)、(7.37±3.40)mmol/L(t=-12.969,P=0.000)。造模后第8周,模型组小鼠的血清TC和TG水平分别为(3.83±0.06)和(2.20±0.20)mmol/L,明显高于对照组的(3.10±0.10)(t=11.000,P=0.000)和(0.90±0.10)mmol/L(t=10.070,P=0.000);HDL水平为(2.03±0.06)mmol/L,明显低于对照组的(2.48±0.02)mmol/L(t=11.662,P=0.000);LDL水平上升但差异无统计学意义[(0.34±0.08)mmol/L比(0.26±0.02)mmol/L;t=1.680,P=0.168];Hb A1c含量为(7.30±0.31)%,明显高于对照组的(4.40±0.32)%(t=-11.587,P=0.000)。结论采用高热量饮食与小剂量多次腹腔注射STZ的方法成功建立了2型糖尿病KM小鼠模型。更多还原

【Abstract】 Objective To establish type 2 diabetes mellitus(T2DM) KM mouse models via the combined use of high-calorie diet and multiple administration of low-dose streptozotocin(STZ). Methods Based on the randomized number table,30 KM mice were equally and randomly divided into 2 groups: modeling group and control group. Mice in the modeling group were given foods with high calories for one month and injected with30 mg/kg STZ via the left lower abdominal cavity for 2-4 consecutive days,while mice in the control group were fed with standard maintenance foods and the same dose of citrate buffer solution. The general conditions including food and water intake and mice weight were recorded. Blood glucose level was measured 1,2,4,5,12,and21 weeks after STZ injection. When the glucose level became stabilized,the serum insulin and blood lipids [including total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein(HDL) and low-density lipoprotein(LDL) ],and hemoglobin a1c(Hb A1c) were measured, and oral glucose tolerance test were performed. Results The modeling group had a 100% survival rate. After STZ injection,the body weight of mice in the modeling group reached the peak in the forth week,and later the growth rate decreased,still significantly lower than that of control group mice till the 21stweek(t = 3. 160,P = 0. 006). Their blood glucose level was significantly higher than that of mice before STZ injection and in the control group(all P < 0. 05); as time went on,it was also rising,and it remained high till the 21 stweek [(26. 38 ± 1. 34) mmol/L]. In the 4thweek,the fasting blood glucose of mice in the modeling group was(11. 86 ± 3. 33) mmol/L,which was significantly higher than that of mice in the control group [(6. 37 ± 1. 27) mmol/L](t =-3. 830,P = 0. 002). Fasting serum insulin of mice in the modeling group showed no significant difference compared with control group[(5. 73 ± 0. 24) m U/L vs.(5. 48 ± 0. 32) m U/L; t =-0. 863,P = 0. 416]. Insulin sensitivity index was 0. 0145 ± 0. 0039, which was significantly lower than that(0. 0267 ± 0. 0039) in control group(t =4. 414,P = 0. 003). In the 6thweek,the blood glucose levels of mice in the modeling group were(15. 35 ±1. 82),(26. 45 ± 1. 07),(25. 58 ± 1. 46),and(26. 15 ± 1. 00) mmol/L 0,30,60,and 120 min after oral gavage of D-glucose,which were all significantly higher than those in the control group [(6. 88 ± 1. 75)(t=-8. 203,P = 0. 000),(17. 65 ± 2. 94)(t =-6. 884,P = 0. 000),(13. 18 ± 2. 04)(t =-12. 110,P= 0. 000),and(7. 37 ± 3. 40) mmol/L(t =-12. 969,P = 0. 000) ]. In the 8thweek,serum TC and TG levels of mice in the modeling group were(3. 83 ± 0. 06) and(2. 20 ± 0. 20) mmol/L,which were significantly higher than those in the control group [(3. 10 ± 0. 10)(t = 11. 000,P = 0. 000) and(0. 90 ± 0. 10)mmol/L(t = 10. 070,P = 0. 000) ]. HDL level of mice in the modeling group was(2. 03 ± 0. 06) mmol/L,which was significantly lower than that in the control group [(2. 48 ± 0. 02) mmol/L; t = 11. 662, P =0. 000]. LDL level was increased but showed no significant difference [(0. 34 ± 0. 08) mmol/L vs.(0. 26 ±0. 02) mmol/L](t = 1. 680, P = 0. 168). Hb A1 c content of mice in the modeling group was(7. 30 ±0. 31) %,which was significantly higher than that(4. 40 ± 0. 32) % in the control group(t =-11. 587,P =0. 000). Conclusion KM mice models of T2 DM were successfully established after high-calorie diet and multiple administration of low-dose STZ.更多还原