国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
INTERNATIONAL JOURNAL OF ANESTHESIOLOGY AND RESUSCITATION
2014年
11期
985-990
,共6页
付宝军%李轶聪%刘芳%张永一%赵昱%王传福
付寶軍%李軼聰%劉芳%張永一%趙昱%王傳福
부보군%리질총%류방%장영일%조욱%왕전복
吗啡镇痛耐受%CC趋化因子配体2%脊髓
嗎啡鎮痛耐受%CC趨化因子配體2%脊髓
마배진통내수%CC추화인자배체2%척수
Morphine antinociceptive tolerance%Hemokine (C-Cmotif) ligand 2%Spinal cord
目的 观察脊髓CC趋化因子配体2[chemokine (C-C motif) ligand 2,CCL2)]蛋白在大鼠吗啡镇痛耐受过程中的作用.方法 成功鞘内置管Sprague-Dawley (SD)大鼠按随机数字表法分成10组(每组6只):IgG+吗啡(IgG+MOR)组、CCL2中和抗体+吗啡(CCL2 neutralizine antibody+MOR)组、IgG+生理盐水(IgG+NS)组、CCL2中和抗体+生理盐水(CCL2neutralizine antibody+NS)组、CCL2中和抗体4+吗啡(CCL2 neutralizine antibody 4+MOR)组、IgG4+吗啡(IgG4+MOR)组、IgG4+生理盐水(IgG4+NS)组、CCL2中和抗体8+吗啡(CCL2 neutralizine antibody 8+MOR)组、IgG8+吗啡(IgG8+MOR)组、IgG8+生理盐水(IgG8+NS)组.连续7d鞘内注射吗啡(15 μg)建立吗啡耐受的动物模型.采用50℃热水甩尾潜伏期法(tail flick latency,TFL)和机械反射阈值法(mechanical withdrawal threshold,MWT)观察CCL2在吗啡的镇痛耐受中作用;应用酶联免疫法(enzyme-linked immunosorbent assay,ELISA)检测吗啡耐受过程中脊髓背角CCL2免疫活性表达变化.结果 在吗啡注射3、5、7 d时,与IgG+MOR组大鼠最大镇痛效应百分率(percent of maximal possible potential effect,％MPE)[％MPETFL:3 d(55±6)％、5 d(27±4)％、7 d(17±3)％;％MPENWT:3 d(54±6)％、5 d(27±4)％、7 d(17±4)％]比较,CCL2 neutralizine antibody+MOR组大鼠％MPE明显增加[(％MPETFL:3 d(65±6)％、5 d(47±4)％、7 d(42±4)％;％MPEMWT:3 d(65±5)、5 d(46±4)、7 d(41±4)(P＜0.01)],与IgG4+MOR组[％MPETFL:5 d(27.3±3.6)％、7 d(17±3)％;％MPEMWT:5 d(27±4)％、7 d(17±3)％]比较,CCL2 neutralizine antibody 4+MOR组大鼠％MPE明显增加[％MPETFL:5 d(46±4)％、7 d(43±4)％; ％MPEMWT:5 d(45±4)％、7 d(44±4)％ (P＜0.01)];在吗啡注射9、11 d时,与IgG8 +MOR组[％MPETFL:9 d(16±3)％、11 d(15±4)％;％MPEMWT:9 d(16±3)％、11 d(14±3)％]比较,CCL2 neutralizineantibody 8+MOR组大鼠％MPE明显增加[％MPEFTL:9 d(26±4)％,11 d(36±4)％;％MPEMWT:9 d(26±4)％、11 d(35±4)％(P＜0.05,P＜0.01)],在吗啡注射7d时,与IgG+NS组比较,IgG+MOR组大鼠脊髓背角CCL2的表达明显增加;然而,与IgG+MOR组比较,CCL2 neutralizine antibody+MOR组大鼠脊髓背角CCL2的表达明显减低.结论 脊髓CCL2可能参与吗啡耐受形成和维持,抑制CCL2可能为临床吗啡镇痛耐受提供一种新的治疗.
目的 觀察脊髓CC趨化因子配體2[chemokine (C-C motif) ligand 2,CCL2)]蛋白在大鼠嗎啡鎮痛耐受過程中的作用.方法 成功鞘內置管Sprague-Dawley (SD)大鼠按隨機數字錶法分成10組(每組6隻):IgG+嗎啡(IgG+MOR)組、CCL2中和抗體+嗎啡(CCL2 neutralizine antibody+MOR)組、IgG+生理鹽水(IgG+NS)組、CCL2中和抗體+生理鹽水(CCL2neutralizine antibody+NS)組、CCL2中和抗體4+嗎啡(CCL2 neutralizine antibody 4+MOR)組、IgG4+嗎啡(IgG4+MOR)組、IgG4+生理鹽水(IgG4+NS)組、CCL2中和抗體8+嗎啡(CCL2 neutralizine antibody 8+MOR)組、IgG8+嗎啡(IgG8+MOR)組、IgG8+生理鹽水(IgG8+NS)組.連續7d鞘內註射嗎啡(15 μg)建立嗎啡耐受的動物模型.採用50℃熱水甩尾潛伏期法(tail flick latency,TFL)和機械反射閾值法(mechanical withdrawal threshold,MWT)觀察CCL2在嗎啡的鎮痛耐受中作用;應用酶聯免疫法(enzyme-linked immunosorbent assay,ELISA)檢測嗎啡耐受過程中脊髓揹角CCL2免疫活性錶達變化.結果 在嗎啡註射3、5、7 d時,與IgG+MOR組大鼠最大鎮痛效應百分率(percent of maximal possible potential effect,％MPE)[％MPETFL:3 d(55±6)％、5 d(27±4)％、7 d(17±3)％;％MPENWT:3 d(54±6)％、5 d(27±4)％、7 d(17±4)％]比較,CCL2 neutralizine antibody+MOR組大鼠％MPE明顯增加[(％MPETFL:3 d(65±6)％、5 d(47±4)％、7 d(42±4)％;％MPEMWT:3 d(65±5)、5 d(46±4)、7 d(41±4)(P＜0.01)],與IgG4+MOR組[％MPETFL:5 d(27.3±3.6)％、7 d(17±3)％;％MPEMWT:5 d(27±4)％、7 d(17±3)％]比較,CCL2 neutralizine antibody 4+MOR組大鼠％MPE明顯增加[％MPETFL:5 d(46±4)％、7 d(43±4)％; ％MPEMWT:5 d(45±4)％、7 d(44±4)％ (P＜0.01)];在嗎啡註射9、11 d時,與IgG8 +MOR組[％MPETFL:9 d(16±3)％、11 d(15±4)％;％MPEMWT:9 d(16±3)％、11 d(14±3)％]比較,CCL2 neutralizineantibody 8+MOR組大鼠％MPE明顯增加[％MPEFTL:9 d(26±4)％,11 d(36±4)％;％MPEMWT:9 d(26±4)％、11 d(35±4)％(P＜0.05,P＜0.01)],在嗎啡註射7d時,與IgG+NS組比較,IgG+MOR組大鼠脊髓揹角CCL2的錶達明顯增加;然而,與IgG+MOR組比較,CCL2 neutralizine antibody+MOR組大鼠脊髓揹角CCL2的錶達明顯減低.結論 脊髓CCL2可能參與嗎啡耐受形成和維持,抑製CCL2可能為臨床嗎啡鎮痛耐受提供一種新的治療.
목적 관찰척수CC추화인자배체2[chemokine (C-C motif) ligand 2,CCL2)]단백재대서마배진통내수과정중적작용.방법 성공초내치관Sprague-Dawley (SD)대서안수궤수자표법분성10조(매조6지):IgG+마배(IgG+MOR)조、CCL2중화항체+마배(CCL2 neutralizine antibody+MOR)조、IgG+생리염수(IgG+NS)조、CCL2중화항체+생리염수(CCL2neutralizine antibody+NS)조、CCL2중화항체4+마배(CCL2 neutralizine antibody 4+MOR)조、IgG4+마배(IgG4+MOR)조、IgG4+생리염수(IgG4+NS)조、CCL2중화항체8+마배(CCL2 neutralizine antibody 8+MOR)조、IgG8+마배(IgG8+MOR)조、IgG8+생리염수(IgG8+NS)조.련속7d초내주사마배(15 μg)건립마배내수적동물모형.채용50℃열수솔미잠복기법(tail flick latency,TFL)화궤계반사역치법(mechanical withdrawal threshold,MWT)관찰CCL2재마배적진통내수중작용;응용매련면역법(enzyme-linked immunosorbent assay,ELISA)검측마배내수과정중척수배각CCL2면역활성표체변화.결과 재마배주사3、5、7 d시,여IgG+MOR조대서최대진통효응백분솔(percent of maximal possible potential effect,％MPE)[％MPETFL:3 d(55±6)％、5 d(27±4)％、7 d(17±3)％;％MPENWT:3 d(54±6)％、5 d(27±4)％、7 d(17±4)％]비교,CCL2 neutralizine antibody+MOR조대서％MPE명현증가[(％MPETFL:3 d(65±6)％、5 d(47±4)％、7 d(42±4)％;％MPEMWT:3 d(65±5)、5 d(46±4)、7 d(41±4)(P＜0.01)],여IgG4+MOR조[％MPETFL:5 d(27.3±3.6)％、7 d(17±3)％;％MPEMWT:5 d(27±4)％、7 d(17±3)％]비교,CCL2 neutralizine antibody 4+MOR조대서％MPE명현증가[％MPETFL:5 d(46±4)％、7 d(43±4)％; ％MPEMWT:5 d(45±4)％、7 d(44±4)％ (P＜0.01)];재마배주사9、11 d시,여IgG8 +MOR조[％MPETFL:9 d(16±3)％、11 d(15±4)％;％MPEMWT:9 d(16±3)％、11 d(14±3)％]비교,CCL2 neutralizineantibody 8+MOR조대서％MPE명현증가[％MPEFTL:9 d(26±4)％,11 d(36±4)％;％MPEMWT:9 d(26±4)％、11 d(35±4)％(P＜0.05,P＜0.01)],재마배주사7d시,여IgG+NS조비교,IgG+MOR조대서척수배각CCL2적표체명현증가;연이,여IgG+MOR조비교,CCL2 neutralizine antibody+MOR조대서척수배각CCL2적표체명현감저.결론 척수CCL2가능삼여마배내수형성화유지,억제CCL2가능위림상마배진통내수제공일충신적치료.
Objective To investigate the role of spinal chemokine (C-C motif) ligand 2 (CCL2) in morphine tolerance to analgesia.Methods Male Sprague-Dawley (SD)rats with successful intrathecal catheter were randomly divided into ten groups by means of random number table (n=6):IgG plus morphine group (IgG+MOR),CCL2 neutralizine antibody plus morphine group (CCL2 neutralizine antibody +MOR),IgG plus saline group (IgG +NS),CCL2 neutralizine antibody plus saline group (CCL2 neutralizine antibody +NS),IgG4 plus morphine group (IgG4 +MOR),CCL2 neutralizine antibody4 plus morphine group (CCL2 neutralizine antibody4+MOR),IgG4 plus saline group (IgG4+NS),IgG8 plus morphine group (IgG8+MOR),CCL2 neutralizine antibody8 plus morphine group (CCL2 neutralizine antibody8+MOR),IgG8 plus saline group (IgG8+NS).A rat model of morphine tolerance to analgesia was induced by intrathecal injection of morphine 15 μg once daily for 7 consecutive days.The role of CCL2 in morphine antinociceptive tolerance is explored by tail flick latency (TFL) and mechanical withdrawal threshold (MWT).ELISA was used to evaluate the change in spinal CCL2 immunoreactivity.Results On days 3,5 and 7 after chronic morphine,percent of maximal possible potential effect by TFL (％MPETFL) and percent of maximal possible potential effect by MWT (％MPEMT) were significantly increased in the CCL2 neutralizing antibody plus morphine group [％MPETFL:3 d (65±6)％,5 d (47±4)％,7 d (42± 4)％.％MPEMWT:3 d (65±5)％,5 d (46±4)％,7 d (41±4)％] versus the IgG plus morphine group [％ MPETFL:3 d (55±6)％,5 d (27±4)％,7d (17±3)％.％MPEMT:3d (54±6)％,5d (27±4)％,7d (17±4)％](P＜0.05,P＜0.01),％MPEFL and ％MPEMWT were significantly up-regulated in the CCL2 neutralizine antibody4 plus morphine group [％MPETFL:5 d (46±4)％,7 d (43±4)％,％ MPEMWT:5 d (45±4)％,7 d (44±4)％]versus the IgG4 plus morphine group [％MPETFL:5 d (27±4)％,7 d (17±3)％,％MPEMT:5 d (27±4)％,7 d (17±3)％](P＜0.01).On days 9 and 11 after chronic morphine,％MPETFL and ％MPEMT were significantly up regulated in the CCL2 neutralizine antibody 8 plus morphine group [％MPETFL:9 d (26±4)％,11 d (36±4)％,％MPEMWT:9 d (26± 4)％,11 d (35±4)％] versus the IgG8 plus morphine group [％ MPETFL:9 d (16±3)％,1 1 d (15±4)％,％MPEMWT:9 d (16±3)％,11 d (14±3)％] (P＜0.05,P＜0.01).On day 7 after chronic morphine,CCL2 expression in the IgG plus morphine group compared with the IgG plus saline group was significantly up-regulated,while CCL2 expression in the CCL2 neutralizine antibody plus morphine group compared with IgG plus MOR group was significantly down-regulated.Conclusions CCL2 in the spinal cord is involved in the development and maintenance of morphine tolerance to analgesia.Inhibition of CCL2 may provide a new therapy for morphine tolerance to analgesia.
