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目的利用胃饲酒精和腹腔注射链脲佐菌素(streptozotocin,STZ)建立2型糖尿病神经病理性痛C57BL/6J小鼠模型。方法 80只C57BL/6J小鼠随机分为:对照组(n=15)和实验组(n=65)。对照组每日胃饲生理盐水,12周后单次空腹腹腔注射柠檬酸缓冲液;实验组每日胃饲酒精12周诱导胰岛素抵抗,继以不同剂量链脲佐菌素(40 mg/kg、50 mg/kg、60 mg/kg)腹腔注射1次,于不同时间点分别测体重、血糖、血胰岛素浓度,计算胰岛素抵抗指数、机械缩足阈值和热缩足潜伏期的变化。结果连续胃饲酒精12周后,实验组小鼠体重明显增加,空腹胰岛素浓度升高,胰岛素抵抗指数升高,血糖未升高,机械缩足阈值和热缩足潜伏期无变化。注射STZ后,40 mg/kg剂量组血糖升高但不能长期维持,60 mg/kg剂量组血糖较高,死亡率高;50 mg/kg剂量组血糖中度升高且相对稳定,胰岛素浓度和胰岛素敏感性均降低,其机械缩足阈值和热缩足潜伏期均低于基础值和对照组(P<0.05)。结论连续酒精胃饲12周后联合腹腔注射STZ50 mg/kg可以建立理想的2型糖尿病神经病理性痛小鼠模型。
Objective To establish a C57BL / 6J mouse model of type 2 diabetic neuropathic pain by intragastric administration of alcohol and intraperitoneal injection of streptozotocin (STZ). Methods 80 C57BL / 6J mice were randomly divided into control group (n = 15) and experimental group (n = 65). The rats in the control group were given gastric lavage once a day for 12 weeks and citrate buffer was injected intraperitoneally fast for 12 weeks. The rats in the experimental group were given gastric lavage with alcohol for 12 weeks to induce insulin resistance, followed by different doses of streptozotocin (40 mg / kg, 50 mg / kg, 60 mg / kg) were intraperitoneally injected once. Body weight, blood glucose and blood insulin levels were measured at different time points to calculate the change of insulin resistance index, mechanical contracting threshold and shrinking foot latency. Results After 12 weeks of continuous gastric feeding, the body weight of experimental mice increased significantly, the fasting insulin concentration increased, the insulin resistance index increased, the blood glucose did not rise, and the mechanical contraction threshold and the thermal contraction foot latency did not change. After injection of STZ, the blood glucose of 40 mg / kg dose group increased but could not be maintained for a long time. The high blood glucose and high mortality rate of 60 mg / kg dose group were higher than those of the control group Insulin sensitivity decreased, the mechanical contraction threshold and thermal contraction foot latency were lower than the baseline value and the control group (P <0.05). CONCLUSION: The combination of intraperitoneal injection of STZ 50 mg / kg for 12 weeks after continuous alcohol feeding can establish an ideal model of neuropathic pain in type 2 diabetic mice.