中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2015年
1期
64-67
,共4页
吗啡依赖%物质戒断综合征%蛋白酶体内肽酶复合物%脊髓%脑
嗎啡依賴%物質戒斷綜閤徵%蛋白酶體內肽酶複閤物%脊髓%腦
마배의뢰%물질계단종합정%단백매체내태매복합물%척수%뇌
Morphine dependence%Substance withdrawal syndrome%Proteasome endopeptidase complex%Spinal cord%Brain
目的 探讨急性和慢性吗啡依赖小鼠脑和脊髓20S蛋白酶体活性的变化.方法 雄性ICR小鼠32只,体重25~ 30 g.实验Ⅰ 取小鼠16只,采用随机数字表法分为2组(n=8):对照组(C组)、急性吗啡依赖组(AMD组).实验Ⅱ 取小鼠16只,采用随机数字表法分为2组(n=8):对照组(C组)、慢性吗啡依赖组(CMD组).急性吗啡依赖模型:皮下注射吗啡100 mg/kg,3h后断头处死.慢性吗啡依赖模型:皮下注射吗啡,共4d,剂量依次为20、30、40、50 mg/kg,每日2次(8:00/20:00),第5天(8:00)皮下注射吗啡10 mg/kg,1h后断头处死.C组用等量生理盐水替代吗啡,其余处理同吗啡依赖组.小鼠断头处死后,分别取海马、前额皮层、纹状体和脊髓组织,采用荧光底物测定法分别检测20S蛋白酶体的糜蛋白酶样(ChT-L)、胰蛋白酶样(T-L)和多肽谷氨酰-多肽水解(PGPH)活性.结果 实验Ⅰ 与C组比较,AMD组脊髓20S蛋白酶体PGPH活性减弱,纹状体和前额皮层20S蛋白酶体T-L活性减弱(P<0.05或0.01);2组海马20S蛋白酶体活性比较差异无统计学意义(P>0.05).实验Ⅱ 与C组比较,CMD组脊髓20S蛋白酶体ChT-L和T-L活性减弱,纹状体20S蛋白酶体PGPH活性增强(P<0.05或0.01);2组前额皮层及海马20S蛋白酶体活性比较差异无统计学意义(P>0.05).结论 急性吗啡依赖小鼠脊髓和脑组织20S蛋白酶体活性减弱,慢性吗啡依赖小鼠脊髓20S蛋白酶体活性减弱,纹状体蛋白酶体活性增强,均具有部位和活性类型特异性,以上改变可能与小鼠吗啡依赖的形成有关.
目的 探討急性和慢性嗎啡依賴小鼠腦和脊髓20S蛋白酶體活性的變化.方法 雄性ICR小鼠32隻,體重25~ 30 g.實驗Ⅰ 取小鼠16隻,採用隨機數字錶法分為2組(n=8):對照組(C組)、急性嗎啡依賴組(AMD組).實驗Ⅱ 取小鼠16隻,採用隨機數字錶法分為2組(n=8):對照組(C組)、慢性嗎啡依賴組(CMD組).急性嗎啡依賴模型:皮下註射嗎啡100 mg/kg,3h後斷頭處死.慢性嗎啡依賴模型:皮下註射嗎啡,共4d,劑量依次為20、30、40、50 mg/kg,每日2次(8:00/20:00),第5天(8:00)皮下註射嗎啡10 mg/kg,1h後斷頭處死.C組用等量生理鹽水替代嗎啡,其餘處理同嗎啡依賴組.小鼠斷頭處死後,分彆取海馬、前額皮層、紋狀體和脊髓組織,採用熒光底物測定法分彆檢測20S蛋白酶體的糜蛋白酶樣(ChT-L)、胰蛋白酶樣(T-L)和多肽穀氨酰-多肽水解(PGPH)活性.結果 實驗Ⅰ 與C組比較,AMD組脊髓20S蛋白酶體PGPH活性減弱,紋狀體和前額皮層20S蛋白酶體T-L活性減弱(P<0.05或0.01);2組海馬20S蛋白酶體活性比較差異無統計學意義(P>0.05).實驗Ⅱ 與C組比較,CMD組脊髓20S蛋白酶體ChT-L和T-L活性減弱,紋狀體20S蛋白酶體PGPH活性增彊(P<0.05或0.01);2組前額皮層及海馬20S蛋白酶體活性比較差異無統計學意義(P>0.05).結論 急性嗎啡依賴小鼠脊髓和腦組織20S蛋白酶體活性減弱,慢性嗎啡依賴小鼠脊髓20S蛋白酶體活性減弱,紋狀體蛋白酶體活性增彊,均具有部位和活性類型特異性,以上改變可能與小鼠嗎啡依賴的形成有關.
목적 탐토급성화만성마배의뢰소서뇌화척수20S단백매체활성적변화.방법 웅성ICR소서32지,체중25~ 30 g.실험Ⅰ 취소서16지,채용수궤수자표법분위2조(n=8):대조조(C조)、급성마배의뢰조(AMD조).실험Ⅱ 취소서16지,채용수궤수자표법분위2조(n=8):대조조(C조)、만성마배의뢰조(CMD조).급성마배의뢰모형:피하주사마배100 mg/kg,3h후단두처사.만성마배의뢰모형:피하주사마배,공4d,제량의차위20、30、40、50 mg/kg,매일2차(8:00/20:00),제5천(8:00)피하주사마배10 mg/kg,1h후단두처사.C조용등량생리염수체대마배,기여처리동마배의뢰조.소서단두처사후,분별취해마、전액피층、문상체화척수조직,채용형광저물측정법분별검측20S단백매체적미단백매양(ChT-L)、이단백매양(T-L)화다태곡안선-다태수해(PGPH)활성.결과 실험Ⅰ 여C조비교,AMD조척수20S단백매체PGPH활성감약,문상체화전액피층20S단백매체T-L활성감약(P<0.05혹0.01);2조해마20S단백매체활성비교차이무통계학의의(P>0.05).실험Ⅱ 여C조비교,CMD조척수20S단백매체ChT-L화T-L활성감약,문상체20S단백매체PGPH활성증강(P<0.05혹0.01);2조전액피층급해마20S단백매체활성비교차이무통계학의의(P>0.05).결론 급성마배의뢰소서척수화뇌조직20S단백매체활성감약,만성마배의뢰소서척수20S단백매체활성감약,문상체단백매체활성증강,균구유부위화활성류형특이성,이상개변가능여소서마배의뢰적형성유관.
Objective To investigate the changes in 20S proteasome activities in the brain and spinal cord of acute and chronic morphine-dependent mice.Metbods Male ICR mice,weighing 25-30 g,were used in the study.The experiment was performed in 2 parts.In experiment Ⅰ,16 mice were randomly divided into 5 groups (n =8 each) using a random number table:control group (group C) and acute morphine dependence group (AMD group).In experiment Ⅱ,16 mice were randomly divided into 5 groups (n =8 each) using a random number table:control group (group C) and chronic morphine dependence group (CMD group).Acute morphine dependence was induced with morphine 100 mg/kg injected subcutaneously,and the mice were sacrificed 3 h later.Chronic morphine dependence was induced by increasing doses of morphine for 4 days,the initial dose of morphine was 20 mg/kg injected subcutaneously twice a day and was increased by 10 mg/kg every day,the dose of morphine was 10 mg/kg injected subcutaneously on 5th day,and then the mice were sacrificed 1 h later.In group C,the equal volume of normal saline was given instead,and the other treatments were similar to those previously described in morphine dependence groups.After the mice were sacrificed,the hippocampus,prefrontal cortex,striatum and spinalcord were isolated for determination of 20S proteasome activity,measured as chymotrypsin-like (ChT-L),trypsin-like (T-L) and peptidylglutamyl-like hydrolyzing (PGLH) activities.Results Experiment Ⅰ Compared with C group,PGLH activity in the spinal cord and T-L activity in the striatum or prefrontal cortex were significantly weakened in group AMD.There was no significant difference in 20S proteasome activity in the hippocampus between the two groups.Experiment Ⅱ Compared with C group,ChT-L and T-L activities in the spinal cord were significantly weakened,and PGLH activity in the striatum was enhanced in CMD group.There was no significant difference in 20S proteasome activity in the prefrontal cortex and hippocampus between the two groups.Conclusion 20S proteasome activity in the spinal cord and brain is weakened in acute morphine-dependent mice,20S proteasome activity in the spinal cord is weakened,20S proteasome activity in the striatum is enhanced in chronic morphine-dependent mice,these changes have specificity in terms of position and type of activity,and the changes mentioned above may be related to development of morphine dependence in mice.