CAJ | 학술논문

目的观察慢性吗啡耐受大鼠脊髓背角神经元磷酸化突触素Ⅰ(p-Synapsin Ⅰ)表达的变化.方法雄性SD大鼠45只,体重150～180 g,月龄1～2月,随机分为5组(n=9):假手术组(S组)、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).除S组外,所有大鼠均行鞘内置管,恢复3 d后鞘内给药,NS组给予生理盐水40 μl,M组给予吗啡20 μg,K组给予氯胺酮30μg,M+K组分别给予吗啡20μg及氯胺酮30 μg,2次/d,连续7 d.于给药前(T_0,基础状态)、给药后1、3、5、7 d及停药后1d(T_(1～5))时测定机械缩爪阈值(PWT)与热缩爪潜伏期(PWL),最后一次测定痛阈后处死大鼠,取L3～6脊髓背角,测定p-Synapsin Ⅰ(Ser603)的表达.结果与基础值比较,M组T_(1,2)时PWT升高,T_(4,5)时PWT降低,T1～3时PWL延长,T_5时PWL缩短,M+K组T_(1～5),时PWT升高,PWL延长(P＜0.05).与S组和NS组比较,M组T_(1,2)时PWT升高,T_(4,5)时PWT降低,T1～3时PWL延长,T_5时PWL缩短,M+K组T_(1～5),时PWT升高,PWL延长(P＜0.05),K组PWT和PWL差异无统计学意义(P＞0.05).与M组比较,M+K组T_(2～5)时PWT升高,T_(3～5)时PWL延长(P＜0.05).与S组和NS组比较,M组和M+K组p-Synapsin Ⅰ(Ser603)表达上调(P＜0.05),K组p-Synapsin Ⅰ(Ser603)表达差异无统计学意义(P＞0.05);与M组比较,M+K组p-Synapsin Ⅰ(Ser603)表达下调(P＜0.05).结论脊髓背角神经元Synapsin Ⅰ的磷酸化参与了大鼠慢性吗啡耐受的形成,吗啡促进Synapsin Ⅰ磷酸化的部分机制与激活N-甲基-D-天冬氨酸受体有关.
목적 관찰만성마배내수대서척수배각신경원린산화돌촉소Ⅰ(p-Synapsin Ⅰ)표체적변화.방법 웅성SD대서45지,체중150～180 g,월령1～2월,수궤분위5조(n=9):가수술조(S조)、생리염수조(NS조)、마배조(M조)、록알동조(K조)화마배+록알동조(M+K조).제S조외,소유대서균행초내치관,회복3 d후초내급약,NS조급여생리염수40 μl,M조급여마배20 μg,K조급여록알동30μg,M+K조분별급여마배20μg급록알동30 μg,2차/d,련속7 d.우급약전(T_0,기출상태)、급약후1、3、5、7 d급정약후1d(T_(1～5))시측정궤계축조역치(PWT)여열축조잠복기(PWL),최후일차측정통역후처사대서,취L3～6척수배각,측정p-Synapsin Ⅰ(Ser603)적표체.결과 여기출치비교,M조T_(1,2)시PWT승고,T_(4,5)시PWT강저,T1～3시PWL연장,T_5시PWL축단,M+K조T_(1～5),시PWT승고,PWL연장(P＜0.05).여S조화NS조비교,M조T_(1,2)시PWT승고,T_(4,5)시PWT강저,T1～3시PWL연장,T_5시PWL축단,M+K조T_(1～5),시PWT승고,PWL연장(P＜0.05),K조PWT화PWL차이무통계학의의(P＞0.05).여M조비교,M+K조T_(2～5)시PWT승고,T_(3～5)시PWL연장(P＜0.05).여S조화NS조비교,M조화M+K조p-Synapsin Ⅰ(Ser603)표체상조(P＜0.05),K조p-Synapsin Ⅰ(Ser603)표체차이무통계학의의(P＞0.05);여M조비교,M+K조p-Synapsin Ⅰ(Ser603)표체하조(P＜0.05).결론 척수배각신경원Synapsin Ⅰ적린산화삼여료대서만성마배내수적형성,마배촉진Synapsin Ⅰ린산화적부분궤제여격활N-갑기-D-천동안산수체유관.
Objective To investigate the change in the expression of phosphorylated synapsin Ⅰ in the spinal dorsal horn following chronic morphine tolerance in rats.Methods Forty-five 1-2 month old male SD rats weighing 150-180 g were randomly divided into 5 groups(n = 9 each): group Ⅰ sham operation(group S);groupⅡ normal saline(group NS);group Ⅲ morphine(group M);group Ⅳ Ketamine(group K)and group Ⅴ M+K.An intrathecal(IT)catheter was placed in the subarachnoid space at L3,4 interspace in group Ⅱ-Ⅴ.Animals showing motor or sensory dysfunction after surgery were excluded.Three days after surgery NS 40 μl,morphine20 μg,ketamine 30 μg and morphine 20 μg+ketamine 30 μg were injected IT twice a day for 7 consecutive days in group Ⅱ,Ⅲ,Ⅳ and Ⅴ respectively.50% paw withdrawal threshold(PWT)to mechanical stimulus and paw withdrawal latency(PWL)to noxious thermal stimulus were measured before(T_0,baseline),on the 1st,3rd,5th and 7th day of IT drug administration(T_(1-4))and at 1 day after IT drug administration(T_5).The animals were sacrificed after last pain threshold measurement.The lumbar segment(L_(3-6))was removed for determination of the expression of phosphorylated synapsin Ⅰ protein.Results In group M,PWT to mechanical stimulus was increased at T_(1,2),returned to the baseline level at T,and decreased at T_(4,5),and PWL to noxious thermal stimulus was prolonged at T_(1-3),returned to the baseline level at T_4 and shortened at T_5 as compared to the baseline value at T_0indicating successful establishment of morphine tolerance.In group M+K,PWT to mechanical stimulus was increased and PWL to noxious thermal stimulus was prolonged at T_(1-5) as compared to the baseline value,indicating inhibition of morphine tolerance by ketamine.The expression of phospberylatod synapsin(Ser 603)was significantly higher in group M and M+K than in group S,and was significantly lower in group M+K than in group M.Conclusion The phosphorylated synapsin Ⅰ in the spinal dorsal horn may be involved in the development of chronic morphine tolerance which is partly mediated by NMDA receptor.