地佐辛对大鼠糖尿病神经痛和脊髓背角N R2B 表达的影响

Effects of dezocine on diabetic neuropathic pain and expression of NMDA receptor subunit 2B in spinal dorsal horns of rats

目的：评价地佐辛对大鼠糖尿病神经痛和脊髓背角含2B亚基NMDA受体（NR2B ）表达的影响。方法雄性SD大鼠，4周龄，体重150～170 g ，腹腔注射链脲霉素（STZ ）制备糖尿病神经痛模型大鼠48只，采用随机数字表法分为2组（ n＝24）：糖尿病神经痛组（DNP组）和地佐辛组（D组），另取血糖正常的大鼠24只作为正常对照组（C组）。D组于注射STZ后第2周开始在前腿外侧肌肉注射地佐辛2.52mg/kg ，1次/d ，连续1周。于肌肉注射地佐辛前（T0）、注射第1天（T1）、第3天（T2）、第5天（T3）、第7天（T4）、注射完毕后7 d （T5）时测定后腿机械缩足反应阈（PWT ），并于T4，5时测定结束后分别处死12只大鼠，取脊髓组织，采用免疫组化法和Western blot法测定脊髓背角NR2B蛋白表达，采用RT-PCR法测定脊髓背角NR2B mRNA的表达水平。结果与C组比较，DNP组大鼠T0-5时、D组T0，5时PWT降低，DNP组T4，5时和D组T5时NR2B蛋白及mRNA表达上调（ P＜0.05）；与DNP组比较，D组T1-4时PWT升高，T4时NR2B蛋白及mRNA表达下调（ P＜0.05），T5时上述指标差异无统计学意义（ P＞0.05）；与T4时比较，D组T0，5时PWT降低（ P＜0.05），T5时NR2B蛋白及mRNA表达上调（ P＜0.05）。结论地佐辛可有效缓解大鼠糖尿病神经痛，其机制与抑制脊髓背角NR2B表达有关。

Objective To evaluate the effects of dezocine on diabetic neuropathic pain （DNP ） and expression of NMDA receptor subunit 2B （NR2B） in the spinal dorsal horns of rats .Methods Forty-eight male Sprague-Dawley rats , aged 4 weeks , weighing 150-170 g , with DNP induced by intraperitoneal injection of streptozocin （STZ） 50 mg/kg （successful induction of diabetes was defined as blood glucose 〉16.7 mmol/L） , were randomly divided into 2 groups （ n=24 each） using a random number table：DNP group and dezocine group （group D） .Twenty-four normal rats were chosen and served as normal control group （group C） .In group D , dezocine 2.52 mg/kg was injected intramuscularly once a day for 7 consecutive days starting from 2nd week after STZ injection ,while the rats in DNP and C groups received the equal volume of normal saline .Paw withdrawl threshold （PWT） to mechanical stimulation was measured before dezocine injection （T0 ） ,and on 1st ,3rd ,5th and 7th days after dezocine injection （T1-4 ） and on 7th day after the end of dezocine injection （T5 ） .Twelve rats in each group were sacrificed after measurement of PWT at T4 ,and T5 .The lumbar segments of the spinal cord were removed for determination of NR2B protein expression （by immuno-histochemistry and Western blot ） and NR2B＆nbsp;mRNA expression （by RT-PCR ） in the spinal dorsal horns .Results Compared with group C ,the PWT at T0-5 in group DNP and at T0 and T5 in group D was significantly decreased , and the expression of NR2B protein and mRNA at T4 ,5 in DNP group and at T5 in D group was up-regulated （ P0.05） . The PWT was significantly lower at T0 and T5 ,and the expression of NR2B protein and mRNA was higher at T5 than at T4 in group D （ P〈0.05 ） .Conclusion Dezocine can effectively relieve DNP in rats and inhibition of NR2B expression in the spinal dorsal horns is involved in the mechanism .