瑞芬太尼诱发切口痛大鼠痛觉过敏时脊髓二价金属离子转运体1表达的变化

Changes in expression of spinal divalent metal transporter 1 during remifentanil-induced hyperalgesia in a rat model of incisional pain

目的评价瑞芬太尼诱发切口痛大鼠痛觉过敏时脊髓二价金属离子转运体1（DMT1）表达的变化。方法雄性sD大鼠32只，体重240～260g，2～3月龄，采用随机数字表法分为4组（n=8）：对照组（C组）静脉输注生理盐水0．1ml·kg-1·min-1 60min；切口痛组（I组）建立大鼠切口痛模型，同时静脉输注生理盐水1．0μg．kg-1·min-1 60min；瑞芬太尼组（R组）静脉输注瑞芬太尼1．0μg．kg-1·min-1 60min；切口痛＋瑞芬太尼组（I＋R组）建立大鼠切口痛模型，同时静脉输注瑞芬太尼1．0μg．kg-1·min-1 60min。分别于静脉输注生理盐水或瑞芬太尼前24h、输注结束后6、24和48h（T0-3）时测定机械缩足反应阈（MWT）和热缩足潜伏期（TwL）。最后一次测定痛阂后处死大鼠，取脊髓组织，采用Western blot法和免疫组化法测定铁反应元件阴性二价金属离子转运体1[DMT1（-）IRE]和铁反应元件阳性二价金属离子转运体1[DMT1（＋）IRE]的表达。结果与C组比较，I组、R组和I＋R组T1-3时MWT降低，TwL缩短，脊髓DMT1（-）IRE表达上调（P〈0．05）；与I组和R组比较，I＋R组T1-3时MWT降低，TWL缩短，脊髓DMT1（-）IRE表达上调（P〈0．05）。4组脊髓DMT1（＋）IRE表达比较差异无统计学意义（P〉0．05）。结论瑞芬太尼诱发切口痛大鼠痛觉过敏的机制可能与激活脊髓DMT1（-）IRE有关。

Objective To evaluate the changes in the expression of spinal divalent metal transporter 1 （DMT1） during remifentanil-induced hyperalgesia in a rat model of incisional pain. Methods Thirty- two male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were randomly divided into 4 groups （n = 8 each） using a random number table： control group （group C） , incisional pain group （group I） , remifentanil group （group R） , and incisional pain ＋ remifentanil group （group I＋R）. In group C, normal saline was infused for 60 min at a rate of 0.1 μg.kg-1·min-1 longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the left hindpaw in sevoflurane-anesthetized rats, and normal saline was infused intravenously for 60 rain at a rate of 1.0 μg.kg-1·min-1 at the same time in group I. In group R, remifentanil was infused for 60 min at a rate of 1.0 μg.kg-1·min-1. In group I＋R, the model of incisiona] pain was established, and remifentanil was simultaneously infused for 60 rain at a rate of 1.0 μg.kg-1·min-1. At 24 h before normal saline or remifentanil infusion and 6, 24 and 48 h after the end of infusion （T03） , the mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured. All the rats were sacrificed after the last measurement of pain thresholds, and the spinal cord was removed for determination of DMT1 with/without iron-responsive element [ DMT1 （＋）IRE and DMT1 （-）IRE] expression （by Western blot analysis and immunohistochemistry）. Results Compared with group C, the MWT was significantly decreased, and the TWL was significantly shortened at T1-3, and the expression of spinal DMT1 （-）IRE was significantly up-regulated in I, R and I＋R groups （P〈0.05）. Compared with I and R groups, the MWT was significantly decreased, and TWL was significantly shortened at T1-3, and the expression of spinal DMT1 （-）1RE was significantly up- regulated in group I＋R （P〈0.05）. There was no significant difference in the expression of spinal DMT1 （＋） IRE between the four groups （P〉 0.05 ）. Conclusion Spinal DMT1 （-）IRE activation may be involved in the mechanism underlying remifentanil-induced hyperalgesia in a rat model of incisional pain.