浙江大学学报（医学版）
浙江大學學報（醫學版）
절강대학학보（의학판）
JOURNAL OF ZHEJIANG UNIVERSITY MEDICAL SCIENCES
2009年
4期
392-398
,共7页
刘甬民%祝胜美%王奎荣%陈庆廉%郑跃英
劉甬民%祝勝美%王奎榮%陳慶廉%鄭躍英
류용민%축성미%왕규영%진경렴%정약영
疼痛,手术后/药物疗法%白细胞介素6/血液%曲马朵/投药和剂量%基因,fos%曲马朵/药理学%脊髓%c-fos%IL-6%大鼠
疼痛,手術後/藥物療法%白細胞介素6/血液%麯馬朵/投藥和劑量%基因,fos%麯馬朵/藥理學%脊髓%c-fos%IL-6%大鼠
동통,수술후/약물요법%백세포개소6/혈액%곡마타/투약화제량%기인,fos%곡마타/약이학%척수%c-fos%IL-6%대서
Pain,postoperative/drug ther%Interleukin-6/blood%Tramadol/admin%Genes,fos%Tramadol/Pharmacol%Spinal cord%c-fos protein%Interleukin-6%Rat
目的:在大鼠切口痛模型中研究腹腔注射曲马多对脊髓c-fos蛋白表达和血液IL-6含量的影响.方法:雄性SD大鼠48只,随机分为6组,每组8只,分别为假手术组、切口痛组、术前3个浓度曲马多预处理组(剂量分别为1 mg/kg、10 mg/kg、20 mg/kg)和术后曲马多治疗组(剂量为10 mg/kg).按Brennan法制成大鼠切口痛模型,以von Frey细丝法(机械性痛觉过敏)、热辐射法(热痛觉过敏)和累积疼痛评分法观察疼痛的行为学变化.手术后2 h取脊髓,并以免疫组织化学检测脊髓c-fos表达(Fos蛋白,以FLI阳性神经元表示),ELISA法测定血清IL-6含量.结果:与假手术组比较,在术后2 h时切口痛组大鼠的von Frey纤毛刺激缩爪阈值明显降低(P<0.01),热刺激缩爪潜伏期明显缩短(P<0.01),累积疼痛评分明显升高(P<0.01);与切口痛组比较,曲马多预处理10 mg/kg和20 mg/kg组大鼠的von Frey纤毛刺激缩爪阚值均明显增加(P<0.01),热刺激缩爪潜伏期均明显延长(P<0.01),累积疼痛评分均明显降低(P<0.01),此效应呈剂量依赖性;PT10组大鼠的行为学改变与T10组相似.切口痛组FLI细胞主要分布在Ⅰ～Ⅱ层,曲马多预处理10 mg/kg和20 mg/kg组FLI细胞与切口痛组相比减少.与假手术组比较,切口痛组大鼠脊髓c-fos表达和血液IL-6含量明显增加(P<0.01);与切口痛组比较,曲马多预处理10 mg/kg和20 mg/kg组能使脊髓c-fos表达和血液IL-6含量明显降低(P<0.01),此效应呈剂量依赖性,而术后曲马多治疗组这种抑制作用弱于曲马多预处理10 mg/kg组(P<0.05).与切口痛组比较,曲马多预处理1 mg/kg组的痛阈和脊髓c-fos表达以及血液IL-6含量差异无显著性意义(P>0.05).结论:曲马多能对疼痛引起的脊髓灰质背角FLI阳性神经元增多和血液IL-6含量增加的效应产生剂量依赖性的抑制作用,曲马多预处理效果更强;脊髓灰质背角Ⅰ～Ⅱ层可能是曲马多产生痛觉调制的主要部位.在大鼠切口痛模型中,曲马多的抗伤害作用可能与抑制脊髓c-fos的表达和减少血液IL-6含量有关.
目的:在大鼠切口痛模型中研究腹腔註射麯馬多對脊髓c-fos蛋白錶達和血液IL-6含量的影響.方法:雄性SD大鼠48隻,隨機分為6組,每組8隻,分彆為假手術組、切口痛組、術前3箇濃度麯馬多預處理組(劑量分彆為1 mg/kg、10 mg/kg、20 mg/kg)和術後麯馬多治療組(劑量為10 mg/kg).按Brennan法製成大鼠切口痛模型,以von Frey細絲法(機械性痛覺過敏)、熱輻射法(熱痛覺過敏)和纍積疼痛評分法觀察疼痛的行為學變化.手術後2 h取脊髓,併以免疫組織化學檢測脊髓c-fos錶達(Fos蛋白,以FLI暘性神經元錶示),ELISA法測定血清IL-6含量.結果:與假手術組比較,在術後2 h時切口痛組大鼠的von Frey纖毛刺激縮爪閾值明顯降低(P<0.01),熱刺激縮爪潛伏期明顯縮短(P<0.01),纍積疼痛評分明顯升高(P<0.01);與切口痛組比較,麯馬多預處理10 mg/kg和20 mg/kg組大鼠的von Frey纖毛刺激縮爪闞值均明顯增加(P<0.01),熱刺激縮爪潛伏期均明顯延長(P<0.01),纍積疼痛評分均明顯降低(P<0.01),此效應呈劑量依賴性;PT10組大鼠的行為學改變與T10組相似.切口痛組FLI細胞主要分佈在Ⅰ～Ⅱ層,麯馬多預處理10 mg/kg和20 mg/kg組FLI細胞與切口痛組相比減少.與假手術組比較,切口痛組大鼠脊髓c-fos錶達和血液IL-6含量明顯增加(P<0.01);與切口痛組比較,麯馬多預處理10 mg/kg和20 mg/kg組能使脊髓c-fos錶達和血液IL-6含量明顯降低(P<0.01),此效應呈劑量依賴性,而術後麯馬多治療組這種抑製作用弱于麯馬多預處理10 mg/kg組(P<0.05).與切口痛組比較,麯馬多預處理1 mg/kg組的痛閾和脊髓c-fos錶達以及血液IL-6含量差異無顯著性意義(P>0.05).結論:麯馬多能對疼痛引起的脊髓灰質揹角FLI暘性神經元增多和血液IL-6含量增加的效應產生劑量依賴性的抑製作用,麯馬多預處理效果更彊;脊髓灰質揹角Ⅰ～Ⅱ層可能是麯馬多產生痛覺調製的主要部位.在大鼠切口痛模型中,麯馬多的抗傷害作用可能與抑製脊髓c-fos的錶達和減少血液IL-6含量有關.
목적:재대서절구통모형중연구복강주사곡마다대척수c-fos단백표체화혈액IL-6함량적영향.방법:웅성SD대서48지,수궤분위6조,매조8지,분별위가수술조、절구통조、술전3개농도곡마다예처리조(제량분별위1 mg/kg、10 mg/kg、20 mg/kg)화술후곡마다치료조(제량위10 mg/kg).안Brennan법제성대서절구통모형,이von Frey세사법(궤계성통각과민)、열복사법(열통각과민)화루적동통평분법관찰동통적행위학변화.수술후2 h취척수,병이면역조직화학검측척수c-fos표체(Fos단백,이FLI양성신경원표시),ELISA법측정혈청IL-6함량.결과:여가수술조비교,재술후2 h시절구통조대서적von Frey섬모자격축조역치명현강저(P<0.01),열자격축조잠복기명현축단(P<0.01),루적동통평분명현승고(P<0.01);여절구통조비교,곡마다예처리10 mg/kg화20 mg/kg조대서적von Frey섬모자격축조감치균명현증가(P<0.01),열자격축조잠복기균명현연장(P<0.01),루적동통평분균명현강저(P<0.01),차효응정제량의뢰성;PT10조대서적행위학개변여T10조상사.절구통조FLI세포주요분포재Ⅰ～Ⅱ층,곡마다예처리10 mg/kg화20 mg/kg조FLI세포여절구통조상비감소.여가수술조비교,절구통조대서척수c-fos표체화혈액IL-6함량명현증가(P<0.01);여절구통조비교,곡마다예처리10 mg/kg화20 mg/kg조능사척수c-fos표체화혈액IL-6함량명현강저(P<0.01),차효응정제량의뢰성,이술후곡마다치료조저충억제작용약우곡마다예처리10 mg/kg조(P<0.05).여절구통조비교,곡마다예처리1 mg/kg조적통역화척수c-fos표체이급혈액IL-6함량차이무현저성의의(P>0.05).결론:곡마다능대동통인기적척수회질배각FLI양성신경원증다화혈액IL-6함량증가적효응산생제량의뢰성적억제작용,곡마다예처리효과경강;척수회질배각Ⅰ～Ⅱ층가능시곡마다산생통각조제적주요부위.재대서절구통모형중,곡마다적항상해작용가능여억제척수c-fos적표체화감소혈액IL-6함량유관.
Objective: To investigate effect of tramadol on c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats. Methods: The Brennan pain model was induced by incision on the planter surface of left hind paw in rats.Forty-eight rats were randomly divided into six groups:Sham group (Group C),control group (Group Ⅰ,pretreatment with saline 5 ml),three tramadol pretreatment groups (Group T1,T10 and T20,pretreated with 1 mg/kg,10 mg/kg and 20 mg/kg tramadol,respectively) and one tramadol treatment group (Group PT10,treated with tramadol 10 mg/kg immediately after operation).Pain behavior was assessed by withdrawal threshold to von Frey filament stimulation intensity,response latency of the hind paw to radiant thermal and a cumulative pain score 2 h after incision.Fos-positive neurons in spinal cord were identified by the immunohistochemical technique.Serum IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Withdrawal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal in Group Ⅰ were significantly lower than those in Group C (P<0.01).Cumulative pain score in Group Ⅰ was significantly higher than that in Group C (P<0.01).In Groups of T10 and T20,withdrawal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal were significantly higher than those in Group Ⅰ (P<0.01),cumulative pain score was significantly lower than that in Group Ⅰ in a dose-dependent manner (P<0.01),and were also those in Group PT10.The greatest density of Fos-positive neurons was located in lamine Ⅰ-Ⅱ in Group Ⅰ.Serum IL-6 levels were significantly elevated in Group Ⅰ.Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1.Administration of tramadol postoperatively also suppressed the c-fos expression and serum IL-6 production as showed in PT10 but were weaker than those in Group T10. Conclusions: Pretreatment with tramadol can produce dose-dependent inhibitory effect on c-fos expression in spinal cord dorsal horn and then suppress the inflammatory response to the trauma.
