氯胺酮鞘内注射对慢性坐骨神经损伤大鼠脊髓NMDA-2B 蛋白表达的影响

目的探讨氯胺酮(KET)连续鞘内注射对慢性坐骨神经挤压损伤大鼠脊髓背角N-甲基-D-天冬氨酸亚基(NMDA-2B,即NR2B)蛋白表达的影响。方法雄性SD大鼠18只,随机分为假手术组、坐骨神经损伤组(CCI组)和CCI KET组。按Bennett等法制作CCI模型,分别以von-Frey纤维丝和冷水测定痛阈及冷刺激反应,采用免疫组化技术测定各组脊髓背角NR2B蛋白表达的变化。结果CCI组痛阈显著下降,冷刺激反应显著升高,脊髓背角有大量NR2B免疫阳性蛋白表达(P<0.01);CCI KET组出现轻度痛敏症状,NR2B阳性蛋白表达受到明显抑制(P<0.01)。结论NR2B蛋白表达上调可能是神经损伤后出现慢性疼痛的发病机制之一,KET通过抑制其表达从而发挥一定程度镇痛作用。

Effect of Intrathecal Ketamine Injection on the Expresstion of NMDA-2B Protein in the Spinal Cord on Rat Models by Chronic Constriction Injury

Objective To evaluate the effect of intrathecal ketamine(KET) on the expression of NR2B protein in the spinal cord of chronic constrction injury(CCI) rats.Methods Eighteen male Spragru-Dawley rats were randomly divided into 3 groups: In sham operation group the animals were shamly operated;In CCI group the rats were placed four loose ligatures around the right sciatic nerve;In CCI KET group ketamine 1 mg/kg was administered 30 min before and 1,2,3,5,7,9,11 days after operation.Rats were tested for hyperalgesia by measuring paw withdrawal latency(PWL) using von-Frey filaments and ice-cold water.The changes in NR2B protein expression in the spinal cord was detected by immuno-histochemical techniques.Results The expression of NR2B protein in the spinal cord was minimal in sham operation group;CCI induced significant increase in the expression of NR2B protein in the ipsilateral spinal cord and ketamine intrathecal significantly inhibited the increase in NR2B protein expression.There was significant difference between sham group with CCI and CCI KET groups(P<0.01).Conclusions Upregulation of NR2B expression may be involved in the development of neuropathic pain and inhibition of NR2B expression may contribute to the antinociceptive effects of ketamine.