Ⅱ型糖尿病神经病理性痛大鼠模型的建立

ESTABLISHING THE MODEL OF TYPE 2 DIABETIC NEUROPATHIC PAIN IN RATS

目的:建立Ⅱ型糖尿病神经病理性痛大鼠模型。方法:60只SD大鼠随机分为:A组(对照组,即普通饲料组,n=10),B组(实验组,即高脂高糖组,n=50)。A组以普通饲料喂养,8周后单次空腹腹腔注射柠檬酸缓冲液。B组高脂高糖喂养8周诱发胰岛素抵抗,继以不同剂量链脲佐菌素(streptozotocin,STZ,30 mg/kg、35 mg/kg、40 mg/kg)腹腔注射1次,于不同时间点分别测体重、血糖、胰岛素,计算胰岛素敏感性、机械缩足阈值和热缩足潜伏期的变化。结果:高脂高糖饮食8周,模型组大鼠体重明显增加,空腹胰岛素浓度升高,胰岛素敏感性下降,机械缩足阈值和热缩足潜伏期无变化,血糖未升高。注射STZ后,30 mg/kg剂量组血糖升高但不能长期维持;40 mg/kg剂量组血糖较高,死亡率高;35 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:高脂高糖饲料喂养8周后联合腹腔注射STZ 35 mg/kg可以建立理想的Ⅱ型糖尿病神经病理性痛大鼠模型。

Objective： To establish the model of type 2 diabetic neuropathic pain in rats. Methods： 60 SD rats were randomly divided into two groups： group A （control group, normal diet group, n = 10）, group B （experiment group, high fat and high glucose group, n = 50）. The rats in group A were fed on normal diet for 8 weeks, and then were injected intraperitoneally with citrate buffer. The rats in group B were fed on a high fat and high glucose diet for 8 weeks to induce insulin resistance, and then were injected intraperitone- ally with different doses of streptozotocin （STZ, 30 mg/kg, 35 mg/kg, 40 mg/kg） once. The changes of body weight, fasting plasma glucose （FPG）, fasting plasma insulin （FINS） and insulin sensitive index （ISI）, mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were determined at different time before and after injection STZ respectively. Results： The model rats exhibited significantly increasing in body weight, serum insulin level, but ISI was declined. No changes were found in mechanical and thermal withdrawal threshold after 8 weeks high fat and fructose diet. After STZ injection, rats in 30 mg/kg group developed hyperglycemia but could not maintain a long period. Rats in 40 mg/kg group had higher blood glucose and highest mortality. Rats in 35 mg/kg group had stable moderate hyperglycemia, there were lower serum insulin level and insulin sensitivity, and the mechanical withdrawal threshold and thermal withdrawal threshold was significantly lower than that of basal level and control group （P 〈 0.05）. Conclusion： High fat and high sugar feeding for 8 weeks combined with low dose STZ （35 mg/kg） can induce an ideal type 2 diabetic neuropathic pain in rats.