1. 1. 广东省第二人民医院麻醉科,广东,广州,510317
2. 中山大学附属第一医院麻醉科,广东,广州,510080
3. 天津市儿童医院麻醉科,天津,300074
4. 广州市番禺区中心医院,广东,广州,511400
网络首发:2017-01-20,
纸质出版:2017
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常路, 叶芳, 舒海华, 等. 芬太尼诱导的大鼠急性痛觉过敏和脊髓炎性反应有关[J]. 中山大学学报(医学科学版), 2017,38(1).
CHANG Lu, YE Fang, SHU Hai-hua, et al. Fentanyl Induced Acute Hyperalgesia is Associated with Spinal Inflammatory Reaction in Rats[J]. Journal of Sun Yat-sen University (Medical Sciences), 2017, 38(1).
摘要:【目的】探索芬太尼诱导的急性痛觉过敏模型中,大鼠脊髓促炎因子表达的变化。【方法】64只雄性SD大鼠分 为2组(n = 32),实验组(Fentanyl组)皮下注射芬太尼60 μg/Kg共4次,每次间隔15 min,对照组(Normal saline组)皮下注射 生理盐水4 次。于注射前1 d(D-1)、注射后1、2、3、4 h 及1 ~ 5 d 对各组大鼠进行压尾机械伤害阈值(Tail flick threshold, TFT)和足底热伤害潜时(Paw withdrawal latency,PWL)两项疼痛行为学测试。注射前1 d,注射后4 h及1 ~ 4 d每组随机选 取4只大鼠处死,取腰段脊髓,以蛋白印迹法(Western blot)测定NF-κB表达,以酶联免疫吸附法(ELISA)测定PGE2、TNF-α、 IL-1β和IL-6的表达。【结果】①对照组大鼠行为学(TFT和PWL)及脊髓NF-κBp65、PGE2、IL-1β,TNF-α分子水平与基础 值相比无统计学差异。②实验组大鼠注射后1hTFT及PWL值升高至最高水平(高于基础水平),随后下降,在注射后第1天 降低至最低水平(低于基础水平),随后上升,在第3 天恢复至基础水平;脊髓NF-κB、PGE2、IL-1β,TNF-α在注射后4 h、 1 及2 d表达升高,IL-6在注射后4 h及1 d表达升高。【结论】急性皮下注射芬太尼可引起大鼠的热及机械痛觉过敏和脊髓 促炎症因子的升高,且行为学及分子学的改变在时间上平行,提示芬太尼诱导的大鼠痛觉过敏和脊髓炎性反应相关。
Abstract:【Objective】To investigate the change of spinal pro?inflammatory cytokines in a rat model of fentanyl induced acute hyperalgesia。【Methods】64 male SD rats were divided into 2 groups(n=32),fentanyl group and NS group. The rats were subcutaneously injected with fentanyl(60 μg/kg) or normal saline(1.2 mL/kg) 4 times with 15 ? minute intervals. Mechanical nociceptive thresholds and thermal nociceptive latency were measured via the tail pressure test(Tail flick thresholds,TFT) and paw withdrawal test(Paw withdrawal latency,PWL)on the day before,at 1,2,3,and 4 hour and on 1~5 day after injection. 4 rats were killed concomitantly and the lumber spinal cord were harvested to analysis the expression of NF-κB,PGE2,TNF-α,IL-1β,and IL-6. 【Results】There were no significant changes of TFT,PWL and the expression of spinal inflammatory cytokines such as NF- κB, PGE2,IL-1β,and TNF-αcompared to baseline of rats treated with normal saline. The value of TFT ,PWL in fentanyl group raised to the highest(above the baseline)at the 1st hour after fentanyl injections and decreased thereafter,reached the lowest at the 1st day, raised increasinglyand up to baseline on the 3 day after injection. NF-κB,PGE2,IL-1β,and TNF-αincreased at the 4th hour,on 1 and 2 day and IL-6 increased at the 4 hour and onthe 1 day after fentanyl injections.【Conclusion】Subcutaneously injection of fentanyl induced significant mechanical and thermal hyperalgesia and increased spinal pro ? inflammatory cytokines parallelly, indicated that fentanyl induced acute hyperalgesia is associated with spinal inflammatory reaction in rats.
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