天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (2): 135-138.doi: 10.11958/20171030

• 实验研究 • 上一篇    下一篇

Nrf2-自噬通路在大鼠切口痛-瑞芬太尼诱导痛觉过敏中的作用

顾喜燕， 王志宏， 于泳浩△   

  1. 天津医科大学总医院麻醉科， 天津市麻醉学研究所 （邮编300052）
  • 收稿日期:2017-10-09 修回日期:2017-12-12 出版日期:2018-02-15 发布日期:2018-02-15
  • 通讯作者: 于泳浩 E-mail:yuyonghao@126.com
  • 基金资助:
    基于蛋白质组学技术研究氢气治疗脓毒症的分子机制

Effects of Nrf2-autophagy pathway in rats of the incisional pain-remifentanil -induced hyperalgesia

GU Xi-yan, WANG Zhi-hong, YU Yong-hao△   

  1. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300052, China,
  • Received:2017-10-09 Revised:2017-12-12 Published:2018-02-15 Online:2018-02-15

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摘要： 摘要： 目的 探讨切口痛-瑞芬太尼痛敏模型大鼠脊髓内核因子 E2 相关因子 2 （Nrf2） -自噬通路在痛觉过敏中的作用。方法 24 只雄性 SD 大鼠依随机数字表法分为 3 组： 盐水+切口痛组 （I 组）、 切口痛-瑞芬太尼痛敏组 （RI 组）、 Nrf2 激动剂 t-BHQ 组 （t-BHQ 组） ,每组 8 只。I 组和 RI 组建模前分别经尾静脉输注生理盐水 0.1 mL/ （kg·min）和瑞芬太尼 1 μg/ （kg·min）， 连续输注 60 min。t-BHQ 组于输注瑞芬太尼前 0.5 h 腹腔注射 t-BHQ （15 mg/kg）， 12 h 1 次， 连续 4 次， 余处理同 RI 组。3 组输注同时于双侧后足建立 Brennan 切口痛模型。分别于输注前 24 h （T0 ）、 输注后 2 h （T1 ）、 6 h （T2 ）、 24 h （T3 ） 和 48 h （T4 ） 测定大鼠机械刺激缩足阈值 （PWT） 及热刺激缩足潜伏期 （PWL）。测试完毕后将大鼠处死， 取 L4~6 脊髓节段， Western blot 法测定脊髓自噬相关蛋白微管相关蛋白 1 轻链 3Ⅱ （LC3Ⅱ）、 Beclin-1、 Nrf2 及其下游分子血红素氧化酶 1 （HO-1） 表达水平。结果 随着处理时间的延长， 3 组 PWT、 PWL 呈总体下降的趋势。从 T1 开始， 与 I 组相比， RI 组 PWT 下降、 PWL 缩短， T4 时 LC3Ⅱ、 Beclin-1 表达升高、 Nrf2、 HO-1 蛋白表达降低 （P＜0.05）； 与 RI 组相比， tBHQ 组 PWT 升高、 PWL 延长 （P＜0.05）， 同时 Nrf2、 HO-1、 LC3Ⅱ、 Beclin-1 蛋白表达均明显升高 （P＜0.05）。结论 Nrf2-自噬通路的激活可明显改善切口痛-瑞芬太尼诱导的痛觉过敏。

关键词: 关键词： 瑞芬太尼, 痛觉过敏, 脊髓, 自噬, 切口痛, 核因子 E2相关因子 2, 叔丁基对苯二酚

Abstract: Abstract: Objective To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2)-autophagy pathway on the incisional pain-remifentanil-induced hyperalgesia of rat model. Methods Twenty-four male Sprague-Dawley rats were randomly allocated into three groups: saline+incisional pain group (group I), remifentanil+incisional pain group (group RI) and Nrf2 agonist t-BHQ group (group tBHQ), with 8 rats in each group. In group I and RI, normal saline at 0.1 mL/(kg· min) and remifentanilat 1 μg/(kg·min) were respectively infused into caudal vein for 60 min. Rats in group t-BHQ were injected intraperitoneally with Nrf2 agonist t-BHQ (15 mg/kg), the first time at 0.5 h before remifentanil infusion, per 12 h once, 4 times in a row, the rest management was the same as group RI. Brennan incision pain model rats were constructed along with the infusions in the three groups. The thermal paw withdraw latency (PWL) and mechanical paw withdraw threshold (PWT) were measured at 24 h before the infusion (T0) and at 2 h (T1), 6 h (T2), 24 h (T3), 48 h (T4) after the infusion. Rats were sacrificed after the tests, then the L4-6 segments of signal cord were removed and the expression levels of autophagy-related proteins, microtubule associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ), Beclin 1, Nrf2 and Nrf2 downstream molecular hemeoxygenase-1 (HO-1) were detected by Western blot assay. Results The PWT and PWL values were decreased significantly with the prolongation of the processing time in the three groups. Compared with group I, PWL and PWT values were decreased at T1-4, the expression levels of LC3Ⅱ and Beclin-1 were increased while Nrf2 and HO-1 were decreased at T in group RI ( 0.05). While compared with group RI, PWL and PWT values were increased, and the expressions of Nrf2 and HO-1 were increased, LC3Ⅱ and Beclin-1 protein were upregulated in group tBHQ (P＜0.05). Conclusion The activation of Nrf2-autophagy pathway can improve the incisional pain- remifentanil induced hyperalgesia.

Key words: Key words: remifentanil, hyperalgesia, spinal cord, autophagy, incisional pain, Nrf2, t-BHQ