摘要
目的评价自噬在瑞芬太尼诱发切口痛大鼠痛觉过敏中的作用。方法清洁级健康雄性SD大鼠40只，2～3月龄，体重250～280 g，采用随机数字表法分为5组（n＝8）：对照组（C组）、瑞芬太尼组（R组）、切口痛组（I组）、切口痛＋瑞芬太尼组（IR组）和切口痛＋瑞芬太尼＋自噬抑制剂三甲基腺嘌呤组（MA组）。R组尾静脉输注瑞芬太尼1 μg·kg^－1·min^－1，IR组在输注瑞芬太尼10 min时开始建立双后足切口痛模型，MA组于造模前1 h腹腔注射三甲基腺嘌呤15 mg/kg，余处理同IR组，余组给予等容量生理盐水。于输注前24 h、输注后2、6、24和48 h（T0-4）时测定机械缩足反应阈（MWT）及热缩足潜伏期（TWL）；T4时测定痛阈后处死大鼠取L4-6脊髓节段，采用Western blot法测定自噬蛋白微管相关蛋白1轻链3Ⅱ（LC3 Ⅱ）、Beclin-1和P62的表达。结果与C组比较，R组、I组、IR组和MA组T1-4时MWT降低、TWL缩短，R组和IR组T4时脊髓LC3Ⅱ和Beclin-1表达上调，P62表达下调，I组T4时脊髓LC3Ⅱ表达上调，MA组T4时脊髓LC3Ⅱ、Beclin-1表达上调（P〈0.05）；与R组比较，IR组T1-4时MWT降低，TWL缩短，T4时脊髓LC3Ⅱ表达上调（P〈0.05）；与I组比较，IR组T1-4时MWT降低，TWL缩短，T4时脊髓LC3Ⅱ和Beclin-1表达上调，P62表达下调（P〈0.05）；与IR组比较，MA组T1-4时MWT降低，TWL缩短，T4时脊髓LC3Ⅱ和Beclin-1表达下调，P62表达上调（P〈0.05）。结论自噬参与了瑞芬太尼诱发切口痛大鼠痛觉过敏的形成和维持。
Objective To evaluate the role of autophagy in remifentanil-induced hyperalgesia in the rats with incisional pain.Methods Forty pathogen-free healthy male Sprague-Dawley rats, aged 2-3 months, weighing 250-280 g, were divided into 5 groups（n=8 each）using a random number table： control group（group C）, remifentanil group（group R）, incisional pain group（group I）, incisional pain plus remifentanil group（group IR）and incisional pain plus remifentanil plus autophagy inhibitor 3-methyladenine（3-MA）group（group MA）. In group R, remifentanil was infused for 60 min at a rate of 1 μg·kg^-1·min^-1 through the caudal vein.In group IR, a 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of both hindpaws in anesthetized rats at 10 min of remifentanil infusion.In group MA, 3-MA 15 mg/kg was injected intraperitoneally at 1 h before establishment of the model, and the other treatments were similar to those previously described in group IR, while the equal volume of normal saline was given in the other groups.The mechanical paw withdrawal threshold（MWT）and thermal paw withdrawal latency（TWL）were measured at 24 h before infusion and 2, 6, 24 and 48 h after infusion（T0-4）. The rats were sacrificed after the last measurement of pain threshold at T4, and the L4-6 segments of the spinal cord were removed for determination of the expression of microtubule-associated protein 1 light chain 3 Ⅱ（LC3 Ⅱ）, Beclin-1 and P62 by Western blot.Results Compared with group C, the MWT was significantly decreased and the TWL was shortened at T1-4 in R, I, IR and MA groups, the expression of LC3Ⅱ and Beclin-1 was up-regulated, and P62 expression was down-regulated in R and IR groups, the expression of LC3Ⅱ was up-regulated at T4 in group I, and the expression of LC3Ⅱ and Beclin-1 was up-regulated at T4 in group MA（P〈0.05）. Compared with group R, the MWT was significantly decreased and the TWL was shortened at T1-4, and the expression of LC3Ⅱ was up-regulated at T4 in group IR（P〈0.05）. Compared with group I, the MWT was significantly decreased and the TWL was shortened at T1-4, and the expression of LC3Ⅱ and Beclin-1 was up-regulated and P62 expression was down-regulated at T4 in group IR（P〈0.05）. Compared with group IR, the MWT was significantly decreased and the TWL was shortened at T1-4, and the expression of LC3Ⅱ and Beclin-1 was down-regulated and P62 expression was up-regulated at T4 in group MA（P〈0.05）.Conclusion Autophagy is involved in the development and maintenance of remifentanil-induced hyperalgesia in the rats with incisional pain.
作者
顾喜燕
于泳浩
王志宏
陈红光
Gu Xiyan;Yu Yonghao;Wang Zhihong;Chen Hongguang(Department of Anesthesiology, General Hospital of Tianjin Medical University Tianjin Research Institute of Anesthesiology, Tianjin 300052, Chin)
出处
《中华麻醉学杂志》
CSCD
北大核心
2017年第12期1485-1488,共4页
Chinese Journal of Anesthesiology
关键词
自噬
哌啶类
疼痛
手术后
痛觉过敏
Autophagy
Piperidines
Pain, postoperative
Hyperalgesia
