中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2010年
1期
60-63
,共4页
吗啡%药物耐受性%脊髓%兴奋性氨基酸转运体3
嗎啡%藥物耐受性%脊髓%興奮性氨基痠轉運體3
마배%약물내수성%척수%흥강성안기산전운체3
Morphine%Drug tolerance%Spinal cord%Excitatory amino acid transporter 3
目的 观察慢性吗啡耐受大鼠脊髓神经元兴奋性氨基酸转运体3(EAAT3)表达的变化.方法 成年雄性SD大鼠45只,随机分为5组(n=9),除假手术组(S组)外,生理盐水组(NS组)、吗啡组(M组)、氯胺酮组(K组)和吗啡+氯胺酮组(M+K组)均进行鞘内置管,鞘内置管后3 d进行鞘内给药,Ns组鞘内注射生理盐水40 μl,M组给予吗啡20μg,K组给予氯胺酮30μg,M+K组给予吗啡20μg+氯胺酮30μg,2次/d,连续7 d.分别在给药前、给药1、3、5、7 d及停药后1 d时测定50%缩爪阈值(PWT)与辐射热缩爪潜伏期(PWL),最后一次测定痛阈后处死大鼠,分别采用免疫印迹分析和免疫组化法检测脊髓EAAT3的表达水平.结果 与S组比较,M组给药1、3 d时PWT升高,给药7 d及停药后1 d时PWT降低,给药1、3、5 d时PWL延长,停药后1 d时PWL缩短;M+K组给药1、3、5、7 d及停药后1 d时PWT升高,PWL延长,M组和M+K组脊髓EAAT3表达下调(P<0.05);与M组比较,M+K组给药3、5、7 d及停药后1 d时PWT升高,给药5、7 d时及停药后1 d时PWL延长.脊髓EAAT3表达上调(P<0.05).EAAT3主要分布于脊髓背角Ⅰ-Ⅱ层的感觉神经元.结论 脊髓背角神经元EAAT3表达下调参与了大鼠慢性吗啡耐受的形成,吗啡下调EAAT3表达的部分机制与激活N-甲基-D天冬氨酸受体有关.
目的 觀察慢性嗎啡耐受大鼠脊髓神經元興奮性氨基痠轉運體3(EAAT3)錶達的變化.方法 成年雄性SD大鼠45隻,隨機分為5組(n=9),除假手術組(S組)外,生理鹽水組(NS組)、嗎啡組(M組)、氯胺酮組(K組)和嗎啡+氯胺酮組(M+K組)均進行鞘內置管,鞘內置管後3 d進行鞘內給藥,Ns組鞘內註射生理鹽水40 μl,M組給予嗎啡20μg,K組給予氯胺酮30μg,M+K組給予嗎啡20μg+氯胺酮30μg,2次/d,連續7 d.分彆在給藥前、給藥1、3、5、7 d及停藥後1 d時測定50%縮爪閾值(PWT)與輻射熱縮爪潛伏期(PWL),最後一次測定痛閾後處死大鼠,分彆採用免疫印跡分析和免疫組化法檢測脊髓EAAT3的錶達水平.結果 與S組比較,M組給藥1、3 d時PWT升高,給藥7 d及停藥後1 d時PWT降低,給藥1、3、5 d時PWL延長,停藥後1 d時PWL縮短;M+K組給藥1、3、5、7 d及停藥後1 d時PWT升高,PWL延長,M組和M+K組脊髓EAAT3錶達下調(P<0.05);與M組比較,M+K組給藥3、5、7 d及停藥後1 d時PWT升高,給藥5、7 d時及停藥後1 d時PWL延長.脊髓EAAT3錶達上調(P<0.05).EAAT3主要分佈于脊髓揹角Ⅰ-Ⅱ層的感覺神經元.結論 脊髓揹角神經元EAAT3錶達下調參與瞭大鼠慢性嗎啡耐受的形成,嗎啡下調EAAT3錶達的部分機製與激活N-甲基-D天鼕氨痠受體有關.
목적 관찰만성마배내수대서척수신경원흥강성안기산전운체3(EAAT3)표체적변화.방법 성년웅성SD대서45지,수궤분위5조(n=9),제가수술조(S조)외,생리염수조(NS조)、마배조(M조)、록알동조(K조)화마배+록알동조(M+K조)균진행초내치관,초내치관후3 d진행초내급약,Ns조초내주사생리염수40 μl,M조급여마배20μg,K조급여록알동30μg,M+K조급여마배20μg+록알동30μg,2차/d,련속7 d.분별재급약전、급약1、3、5、7 d급정약후1 d시측정50%축조역치(PWT)여복사열축조잠복기(PWL),최후일차측정통역후처사대서,분별채용면역인적분석화면역조화법검측척수EAAT3적표체수평.결과 여S조비교,M조급약1、3 d시PWT승고,급약7 d급정약후1 d시PWT강저,급약1、3、5 d시PWL연장,정약후1 d시PWL축단;M+K조급약1、3、5、7 d급정약후1 d시PWT승고,PWL연장,M조화M+K조척수EAAT3표체하조(P<0.05);여M조비교,M+K조급약3、5、7 d급정약후1 d시PWT승고,급약5、7 d시급정약후1 d시PWL연장.척수EAAT3표체상조(P<0.05).EAAT3주요분포우척수배각Ⅰ-Ⅱ층적감각신경원.결론 척수배각신경원EAAT3표체하조삼여료대서만성마배내수적형성,마배하조EAAT3표체적부분궤제여격활N-갑기-D천동안산수체유관.
Objective To investigate the change in the expression of excitatory amino acid transporter 3 (EAAT3) in the spinal cord neurons in a rat model of chronic morphine tolerance. Methods Forty-five male SD rats were randomly divided into 5 groups ( n = 9 each) : group I sham operation (group S); group II normal saline (group NS); group Ⅰ morphine (group M); group Ⅳ ketamine (group K) and groupV M + K. In group II - V a catheter was placed in the subarachnoid space at L_(3-5) interspace. The animals were observed for 3 days. The animals with motor or sensory paralysis of the hindlimbs were excluded. NS 40 μl,morphine 20 μg, ketamine 30μg,morphine 20μg + ketamine 30μg were injected via intrathecal catheter twice a day for 7 consecutive days. 50% paw withdrawal threshold and latency (PWT, PWL) of the hindpaw to radiant heat were measured before (T_0, baseline) , on day 1, 3, 5, 7 of (T_(1-4)) and 1 day after (T_5 ) IT drug administration. The rats were sacrificed after last pain threshold measurement. The expression of EAAT3 protein in the spinal cord was determined by Western blotting and immuno-histochemistry. Results The sensitivity of the hindpaw to noxious heat stimulation was significantly decreased during (T_(1,2)) and increased after IT administration (T_(4,5)) in group M and was significantly decreased during and after FT administration (T_(1-5)) in group M + K as compared with the baseline values at T_0 and group S and was significant lower in group M + K than in group M. The expression of EAAT3 protein in the spinal cord was significantly decreased in group M and M + K as compared with group S and was significantly lower in group M than in group M + K. Conclusion The down-regulation of the expression of EAAT3 in the spinal dorsal horn neurons is involved in the development of chronic morphine tolerance and the expression of EAAT3 is down-regulated by morphine partly through the activation of NMDA receptor.
