天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (6): 700-703.doi: 10.11958/20150404

• 实验研究 • 上一篇    下一篇

右美托咪定对痛觉过敏大鼠脊髓 PKCγ、 CaMKⅡα及pCaMKⅡα表达的影响

孙哲， 王志芬， 何颖， 王国林， 于泳浩， 元元   

  1. 天津医科大学总医院麻醉科， 天津市麻醉学研究所
  • 收稿日期:2015-12-17 修回日期:2016-01-08 出版日期:2016-06-15 发布日期:2016-07-04
  • 基金资助:
    国家自然科学基金资助项目 （81300960）； 天津市应用基础与前沿技术研究计划 （14JCQNJC12800）

Influence of dexmedetomidine on expressions of PKCγ, CaMKⅡα and pCaMKⅡα in spinal cord in rats with hyperalgesia

SUN Zhe, WANG Zhifen, HE Ying, WANG Guolin, YU Yonghao, YUAN Yuan   

  1. Department of Anesthesiology, the General Hospital of Tianjin Medical University; Tianjin Research Institute of Anesthesiology, Tianjin 300052, China
  • Received:2015-12-17 Revised:2016-01-08 Published:2016-06-15 Online:2016-07-04
  • Contact: Zhe SUN E-mail:sunzhe199203@126.com

PDF (PC)

3915

摘要： 摘要： 目的 探讨右美托咪定对切口痛-瑞芬太尼痛觉过敏大鼠脊髓蛋白激酶 C （PKC） γ、 钙/钙调素依赖性蛋白激酶 （CaMK） Ⅱα及 pCaMKⅡα表达的影响。方法 雄性 SD 大鼠 40 只， 体质量 240~260 g， 2~3 月龄， 随机数字表法分为 5 组 （n=8）： 空白对照组 （C 组）、 瑞芬太尼+切口痛组 （R+I 组）、 右美托咪定+瑞芬太尼+切口痛组 （D+R+I 组）、 右美托咪定+瑞芬太尼+切口痛+佛波醇酯+二甲基亚砜组 （D+R+I+P+DMSO 组）、 右美托咪定+瑞芬太尼+切口痛+二甲基亚砜组（D+R+I+DMSO 组）。采用足底切口的方法制备切口痛模型。瑞芬太尼以 1.2 μg·kg-1·min-1的速度经尾静脉输注 90 min； 右美托咪定以 50 μg/kg 的剂量于术前 30 min 皮下注射； 佛波醇酯及二甲基亚砜均为鞘内注射 10μL。分别于输注前 24 h（T0）、 输注后 2、 6、 24 和 48 h（T1~4）时测定热刺激缩足潜伏期（PWL）和机械刺激缩足阈值（PWT）。最后 1 次行为学测试后处死大鼠， 取脊髓 L4~6节段。采用 Western blot 法测定脊髓背角 PKCγ、 CaMKⅡα及pCaMKⅡα的表达。结果 除 T0外， 与 C 组比较， 其余各组 PWL 缩短、 PWT 降低， PKCγ、 CaMKⅡα及 pCaMKⅡα表达上调。与 R+I 组比较， D+R+I 组、 D+R+I+DMSO 组 PWL 延长、 PWT 升高， PKCγ、 CaMKⅡα及 pCaMKⅡα表达下调。与 D+R+I 组比较， D+R+I+P+DMSO 组 PWL 缩短、 PWT 降低， PKCγ、 CaMKⅡα及 pCaMKⅡα表达上调。与 D+R+I+P+DMSO 组比较， D+R+I+DMSO 组 PWL 延长、 PWT 升高， PKCγ、 CaMKⅡα及 pCaMKⅡα表达下调。结论 右美托咪定可以减少切口痛-瑞芬太尼痛觉过敏大鼠脊髓 PKCγ、 CaMKⅡα及 pCaMKⅡα的表达。

关键词: 痛觉过敏, 脊髓, 蛋白激酶 C, 钙-钙调素依赖性蛋白激酶 2 型, 佛波醇酯类, 大鼠, Sprague-Dawley, 右美托咪定, 瑞芬太尼

Abstract: Abstract： Objective To investigate the influence of dexmedetomidine on expressions of protein kinase c (PKC)γ, calcium/calmodulin-dependent protein kinase (CaMK)Ⅱα and pCaMKⅡα in spinal cord in rats with incisional pain (IP) and remifentanil-induced hyperalgesia. Methods Forty male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g,were randomly divided into 5 groups (n=8 each): blank control group (group C), remifentanil+incisional pain group (group R+I), dexmedetomidine + remifentanil + incisional pain group (group D+R+I), dexmedetomidine + remifentanil + incisional pain + phorbol myristate acetate + DMSO group (group D+R+I+P+DMSO) and dexmedetomidine + remifentanil + incisional pain + DMSO group (group D+R+I+ DMSO). The incisional pain rat model was established by a plantar incision in left hind paw. Remifentanil was infused at a rate of 1.2 μg·kg-1·min-1 for 90 min via the caudal vein. Dexmedetomidine was adminis⁃ tered subcutaneously at a dose of 50 μg/kg at 30 min before plantar incision. Phorbol myristate acetate and DMSO were intrathecally injected at a dose of 10 μL. Paw withdrawal latency (PWL) to thermal stimulation and paw withdrawal threshold (PWT) to von Frey hair stimulation were measured 24 h before remifentanil infusion (T0) and at 2, 6, 24 and 48 h (T1-4) after intraveonus remifentanil injection. The rats were sacrificed after the last behavioral test and the L4- 6 segment of spinal cord was removed to determine the expressions of PKCγ, CaMKⅡα and pCaMKⅡα in spinal cord by Western blot analysis. Re⁃sults Compared with group C, the value of PWL was significantly shortened and PWT was significantly decreased except T0, and the expressions of PKCγ, CaMKⅡα and pCaMKⅡα were up-regulated in other groups. Compared with group R+I,the value of PWL was significantly prolonged and PWT was significantly increased, the expressions of PKCγ, CaMKⅡα and pCaMKⅡα were down-regulated in group D+R+I and group D+R+I+DMSO. Compared with group D+R+I, the value of PWL was significantly shortened and PWT was significantly decreased, the expressions of PKCγ, CaMKⅡα and pCaMKⅡα were up-regulated in group D+R+I+P+DMSO. Compared with group D+R+I+P+DMSO, the value of PWL was significantly prolonged and PWT was significantly increased, the expressions of PKCγ, CaMKⅡα and pCaMKⅡα were down-regulated in group D+R+I+DMSO. Conclusion Dexmedetomidine can reduce the expressions of PKCγ, CaMKⅡα and pCaMKⅡα in spinal cord in rats with IP and hyperalgesia induced by remifentanil.

Key words: hyperalgesia, spinal cord, protein kinase C, calcium-calmodulin-dependent protein kinase type 2, phorbol esters, rats, Sprague-Dawley, Dexmedetomidine, Remifentanil