氟比洛芬酯对切口痛大鼠行为学及大鼠脊髓背角Fos蛋白表达的影响
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摘要
目的:(1)通过复制切口痛大鼠模型,拟从行为学方面来探讨应用氟比洛芬酯术后镇痛的可行性;(2)应用免疫组织化学的方法,观察氟比洛芬酯对切口痛大鼠脊髓c-fos蛋白表达的影响,以探讨氟比洛芬酯的超前镇痛作用。
方法:32只清醒大鼠随机分为4组,每组8只。空白对照组:未进行任何处理的对照组;脂微球组:经大鼠尾静脉注射3ml/kg脂微球注射液15min后吸入异氟醚麻醉后进行手术;术前干预组:经大鼠尾静脉注射30mg/kg氟比洛芬酯15min后进行手术;术后干预组:手术后15min经大鼠尾静脉注射30mg╱kg氟比洛芬酯。按照Brennan法建立外科手术痛大鼠模型,待大鼠清醒后采用累积疼痛评分法,评定术后大鼠0—60分钟12个时段内疼痛行为的变化。术后1.5小时将大鼠处死,灌注,取脊髓腰膨大段,用免疫组化的方法测定脊髓背角c-fos蛋白的表达。
结果:(1)空白对照组大鼠未进行外科手术大鼠无行为学变化,活动如常,双后爪着地且负重,疼痛累积评分为0.17±0.75;脂微球组大鼠外科手术后表现舔,抬高术侧后爪行为,偶尔着地且极少负重,疼痛累积评分为18.00±1.41;术前干预组及术后干预组疼痛累积评分均较空白对照组明显增高,较脂微球组明显降低,差异有显著性(P＜0.05);术前干预组和术后干预组比较,术前干预组疼痛评分较低,差异有显著性(P＜0.05)。(2)外科手术切口诱发的Fos免疫样(fos like immunoreactive,FLI)阳性神经元主要位于手术切口同侧的脊髓灰质背角Ⅰ,Ⅱ和Ⅴ,Ⅵ层。空白对照组大鼠未进行外科手术,脊髓FLI阳性细胞数目较少。脂微球组经过外科手术,手术侧脊髓L4-L5节段灰质出现大量FLI阳性神经元,最多分布在脊髓背角浅层(Ⅰ-Ⅱ层),其次在颈部(Ⅴ-Ⅵ层),固有核和腹侧灰质也有少量FLI阳性神经元。术前干预组和术后干预组大鼠脊髓灰质背角FLI阳性细胞数目较脂微球组有减少的趋势,且与脂微球组有显著性差异(P＜0.05)。术前干预组和术后干预组之间比较,术前干预组大鼠脊髓灰质背角FLI阳性细胞数目较少(P＜0.05)。
结论:(1)氟比洛芬酯对切口痛大鼠的伤害性行为有一定程度的抑制作用;(2)氟比洛芬酯能减少脊髓背角c-fos蛋白表达,抑制脊髓背角神经元对伤害刺激的反应,具有超前镇痛的作用。
Objectives:(1)To study the feasibility of postoperative analgesia of the flurbiprofen axetil through nociceptive behaviors in the incision-induced rats;(2)To observe the expression of Fos in the spina dorsal horn in the incision-induced rats so as to investigate the preemptive analgesia of flurbiprofen axetil.
Methods:32 awake rats weighing 140-190g were randomly divided into four groups,each group included 8 rats.Normal controlling group: isoflurane was inhaled for 5 min but no incision was made;Lipoid microballoon group:vena caudalis injected Lipoid microballoon 3ml/kg 15 min prior to the incision in the plantar of the right hind paw;Preoperative administration group:vena caudalis injected flurbiprofen axetil 30mg/kg 15 min prior to the incision;Postoperative administration group:vena caudalis injected flurbiprofen axetil 30mg/kg 15 min inferior to the incision.Incision of 1 cm long was made in the plantar region of left hindpaw parallel to the muscle under isoflurane anesthesia according to the method of Brennan. Pain behavior was assessed by a cumulative pain score.Stepping behavior was evaluated 0-60 min after hind paw incision.One and half an hour later, rats were extracted blood from heart then perfused,L4-L5 sections of spinal cords were dissected,sliced and processed by immunostained with a rabbit polyclonal antiserum directed against c-fos.The changes of FLI positive neurons in the dorsal horn were studied.
Results:(1)Rats in the normal controlling group which no incision was made had not changes of behavior.The cumulative pain score were 0.17±0.75.Rats in the lipoid microballoon group the cumulative pain score were 18.00±1.41.The cumulative pain score were significantly increased after plantar incision in the preoperative and postoperative administration group(P<0.05)compared with the normal controlling group,and significantly decreased compared with the lipoid microballoon group (P<0.05).The cumulative pain score of the preoperative administration group was lower than the postoperative administration group and the difference was significant(P<0.05).(2)Incision-induced FLI positive neurons were mainly distributed in the incision ipsilateral laminaⅠ,ⅡandⅤ,Ⅵof spinal dorsal horn.Rats in the normal controlling group in which no incision was made the average numbers of FLI positive neuron were the least.In the lipoid microballoon group,lots of FLI positive neurons were observed in the ipsilateral spinal dorsal horn of L4-L5 to the incision.The most of them were located in the lamina superficialis of spinal dorsal horn.The average numbers of FLI positive neuron in the spinal dorsal horn of the preoperative and postoperative administration group were less than the lipoid microballoon group and the differences were significant(P<0.05).The average numbers of FLI positive neuron in the spinal dorsal horn of preoperative administration group was significantly less compared to postoperative administration group(P<0.05).
Conclusion:(1)To the extent the incision-evoked nociceptive behaviors were suppressed by administration of flurbiprofen axetil;(2) Flurbiprofen axetil can suppress the expression of c-fos in the spinal dorsal horn and the response of spinal dorsal horn neuron to the harmgul stimulus. Flurbiprofen axetil has the effects of preemptive analgesia.
方法:32只清醒大鼠随机分为4组,每组8只。空白对照组:未进行任何处理的对照组;脂微球组:经大鼠尾静脉注射3ml/kg脂微球注射液15min后吸入异氟醚麻醉后进行手术;术前干预组:经大鼠尾静脉注射30mg/kg氟比洛芬酯15min后进行手术;术后干预组:手术后15min经大鼠尾静脉注射30mg╱kg氟比洛芬酯。按照Brennan法建立外科手术痛大鼠模型,待大鼠清醒后采用累积疼痛评分法,评定术后大鼠0—60分钟12个时段内疼痛行为的变化。术后1.5小时将大鼠处死,灌注,取脊髓腰膨大段,用免疫组化的方法测定脊髓背角c-fos蛋白的表达。
结果:(1)空白对照组大鼠未进行外科手术大鼠无行为学变化,活动如常,双后爪着地且负重,疼痛累积评分为0.17±0.75;脂微球组大鼠外科手术后表现舔,抬高术侧后爪行为,偶尔着地且极少负重,疼痛累积评分为18.00±1.41;术前干预组及术后干预组疼痛累积评分均较空白对照组明显增高,较脂微球组明显降低,差异有显著性(P＜0.05);术前干预组和术后干预组比较,术前干预组疼痛评分较低,差异有显著性(P＜0.05)。(2)外科手术切口诱发的Fos免疫样(fos like immunoreactive,FLI)阳性神经元主要位于手术切口同侧的脊髓灰质背角Ⅰ,Ⅱ和Ⅴ,Ⅵ层。空白对照组大鼠未进行外科手术,脊髓FLI阳性细胞数目较少。脂微球组经过外科手术,手术侧脊髓L4-L5节段灰质出现大量FLI阳性神经元,最多分布在脊髓背角浅层(Ⅰ-Ⅱ层),其次在颈部(Ⅴ-Ⅵ层),固有核和腹侧灰质也有少量FLI阳性神经元。术前干预组和术后干预组大鼠脊髓灰质背角FLI阳性细胞数目较脂微球组有减少的趋势,且与脂微球组有显著性差异(P＜0.05)。术前干预组和术后干预组之间比较,术前干预组大鼠脊髓灰质背角FLI阳性细胞数目较少(P＜0.05)。
结论:(1)氟比洛芬酯对切口痛大鼠的伤害性行为有一定程度的抑制作用;(2)氟比洛芬酯能减少脊髓背角c-fos蛋白表达,抑制脊髓背角神经元对伤害刺激的反应,具有超前镇痛的作用。
Objectives:(1)To study the feasibility of postoperative analgesia of the flurbiprofen axetil through nociceptive behaviors in the incision-induced rats;(2)To observe the expression of Fos in the spina dorsal horn in the incision-induced rats so as to investigate the preemptive analgesia of flurbiprofen axetil.
Methods:32 awake rats weighing 140-190g were randomly divided into four groups,each group included 8 rats.Normal controlling group: isoflurane was inhaled for 5 min but no incision was made;Lipoid microballoon group:vena caudalis injected Lipoid microballoon 3ml/kg 15 min prior to the incision in the plantar of the right hind paw;Preoperative administration group:vena caudalis injected flurbiprofen axetil 30mg/kg 15 min prior to the incision;Postoperative administration group:vena caudalis injected flurbiprofen axetil 30mg/kg 15 min inferior to the incision.Incision of 1 cm long was made in the plantar region of left hindpaw parallel to the muscle under isoflurane anesthesia according to the method of Brennan. Pain behavior was assessed by a cumulative pain score.Stepping behavior was evaluated 0-60 min after hind paw incision.One and half an hour later, rats were extracted blood from heart then perfused,L4-L5 sections of spinal cords were dissected,sliced and processed by immunostained with a rabbit polyclonal antiserum directed against c-fos.The changes of FLI positive neurons in the dorsal horn were studied.
Results:(1)Rats in the normal controlling group which no incision was made had not changes of behavior.The cumulative pain score were 0.17±0.75.Rats in the lipoid microballoon group the cumulative pain score were 18.00±1.41.The cumulative pain score were significantly increased after plantar incision in the preoperative and postoperative administration group(P<0.05)compared with the normal controlling group,and significantly decreased compared with the lipoid microballoon group (P<0.05).The cumulative pain score of the preoperative administration group was lower than the postoperative administration group and the difference was significant(P<0.05).(2)Incision-induced FLI positive neurons were mainly distributed in the incision ipsilateral laminaⅠ,ⅡandⅤ,Ⅵof spinal dorsal horn.Rats in the normal controlling group in which no incision was made the average numbers of FLI positive neuron were the least.In the lipoid microballoon group,lots of FLI positive neurons were observed in the ipsilateral spinal dorsal horn of L4-L5 to the incision.The most of them were located in the lamina superficialis of spinal dorsal horn.The average numbers of FLI positive neuron in the spinal dorsal horn of the preoperative and postoperative administration group were less than the lipoid microballoon group and the differences were significant(P<0.05).The average numbers of FLI positive neuron in the spinal dorsal horn of preoperative administration group was significantly less compared to postoperative administration group(P<0.05).
Conclusion:(1)To the extent the incision-evoked nociceptive behaviors were suppressed by administration of flurbiprofen axetil;(2) Flurbiprofen axetil can suppress the expression of c-fos in the spinal dorsal horn and the response of spinal dorsal horn neuron to the harmgul stimulus. Flurbiprofen axetil has the effects of preemptive analgesia.
引文
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[2]Vaughan RS.Pain relief after thoracotomy.Br J Anaesth,2001,87(5):681-683.
[3]Aoki H,Satomoto M,Yamada S,et al.The effectiveness of perioperative intravenous flurbiprofen in minor ear,neck and nose surgery[J].Masui,2002,51(8):857-861
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[5]方向义,胡海涛.中枢神经系统Fos蛋白的表达,与外周伤害性刺激.神经解剖学杂志,1996,(3)
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