中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2010年
3期
334-336
,共3页
卫毅%石翊飒%张双银%马永丰
衛毅%石翊颯%張雙銀%馬永豐
위의%석익삽%장쌍은%마영봉
受体,N-甲基-D-天冬氨酸%寡核苷酸类,反义%注射,脊髓%吗啡依赖%纳洛酮%物质戒断综合征
受體,N-甲基-D-天鼕氨痠%寡覈苷痠類,反義%註射,脊髓%嗎啡依賴%納洛酮%物質戒斷綜閤徵
수체,N-갑기-D-천동안산%과핵감산류,반의%주사,척수%마배의뢰%납락동%물질계단종합정
Receptors,N-methyl-D-aspartate%Oligonucleotides,antisense%Injections,spinal%Morphine dependence%Naloxone%Substance withdrawal syndrome
目的 评价鞘内注射N-甲基-D-天门冬氨酸(NMDA)受体2B亚基(NR2B)反义寡核苷酸对纳洛酮诱发吗啡依赖大鼠戒断反应的影响.方法 健康雌性SD大鼠,体重230～270 g,腹腔注射戊巴比妥钠60mg/kg麻醉下,于L3,4间隙穿刺置管.取鞘内置管成功的大鼠32只,随机分为4组(n=8):对照组(C组)、吗啡依赖组(MD组)、反义寡核苷酸组(AO组)和正义寡核苷酸组(SO组).MD组、AO组和SO组皮下注射吗啡10 mg/kg,2次/d,隔天增加10 mg/kg,至第6天末次注射50 mg/kg,建立吗啡依赖模型;C组皮下注射等量生理盐水.AO组和SO组于注射吗啡的同时分别鞘内注射15 nmol NR2B的反义寡核苷酸和正义寡核苷酸,用生理盐水稀释至5μl;C组和MD组鞘内注射等量生理盐水.各组在末次注射吗啡或生理盐水后4 h时,腹腔注射纳洛酮4 mg/kg诱发吗啡戒断.给予纳洛酮后30 min内观察戒断反应,并进行评分.计算大鼠体重变化幅度.给予纳洛酮后1 h时处死大鼠,测定海马NR1、NR2A和NR2B的mRNA表达水平.结果 与C组比较,MD组、AO组和SO组戒断反应评分和体重变化幅度升高,MD组和SO组海马组织NR2B mRNA表达上调(P<0.05或0.01);与MD组比较,AO组戒断反应评分和体重变化幅度降低,海马组织NR2A mBNA表达上调,NR2B mRNA表达下调(P<0.05或0.01),SO组各指标差异无统计学意义(P>0.05).各组海马组织NR1 mRNA表达比较差异无统计学意义(P>0.05).结论 鞘内注射NR2B反义寡核苷酸可抑制纳洛酮诱发吗啡依赖大鼠戒断反应,其机制与海马NMDA受体亚基水平和构成的变化调节有关.
目的 評價鞘內註射N-甲基-D-天門鼕氨痠(NMDA)受體2B亞基(NR2B)反義寡覈苷痠對納洛酮誘髮嗎啡依賴大鼠戒斷反應的影響.方法 健康雌性SD大鼠,體重230～270 g,腹腔註射戊巴比妥鈉60mg/kg痳醉下,于L3,4間隙穿刺置管.取鞘內置管成功的大鼠32隻,隨機分為4組(n=8):對照組(C組)、嗎啡依賴組(MD組)、反義寡覈苷痠組(AO組)和正義寡覈苷痠組(SO組).MD組、AO組和SO組皮下註射嗎啡10 mg/kg,2次/d,隔天增加10 mg/kg,至第6天末次註射50 mg/kg,建立嗎啡依賴模型;C組皮下註射等量生理鹽水.AO組和SO組于註射嗎啡的同時分彆鞘內註射15 nmol NR2B的反義寡覈苷痠和正義寡覈苷痠,用生理鹽水稀釋至5μl;C組和MD組鞘內註射等量生理鹽水.各組在末次註射嗎啡或生理鹽水後4 h時,腹腔註射納洛酮4 mg/kg誘髮嗎啡戒斷.給予納洛酮後30 min內觀察戒斷反應,併進行評分.計算大鼠體重變化幅度.給予納洛酮後1 h時處死大鼠,測定海馬NR1、NR2A和NR2B的mRNA錶達水平.結果 與C組比較,MD組、AO組和SO組戒斷反應評分和體重變化幅度升高,MD組和SO組海馬組織NR2B mRNA錶達上調(P<0.05或0.01);與MD組比較,AO組戒斷反應評分和體重變化幅度降低,海馬組織NR2A mBNA錶達上調,NR2B mRNA錶達下調(P<0.05或0.01),SO組各指標差異無統計學意義(P>0.05).各組海馬組織NR1 mRNA錶達比較差異無統計學意義(P>0.05).結論 鞘內註射NR2B反義寡覈苷痠可抑製納洛酮誘髮嗎啡依賴大鼠戒斷反應,其機製與海馬NMDA受體亞基水平和構成的變化調節有關.
목적 평개초내주사N-갑기-D-천문동안산(NMDA)수체2B아기(NR2B)반의과핵감산대납락동유발마배의뢰대서계단반응적영향.방법 건강자성SD대서,체중230～270 g,복강주사무파비타납60mg/kg마취하,우L3,4간극천자치관.취초내치관성공적대서32지,수궤분위4조(n=8):대조조(C조)、마배의뢰조(MD조)、반의과핵감산조(AO조)화정의과핵감산조(SO조).MD조、AO조화SO조피하주사마배10 mg/kg,2차/d,격천증가10 mg/kg,지제6천말차주사50 mg/kg,건립마배의뢰모형;C조피하주사등량생리염수.AO조화SO조우주사마배적동시분별초내주사15 nmol NR2B적반의과핵감산화정의과핵감산,용생리염수희석지5μl;C조화MD조초내주사등량생리염수.각조재말차주사마배혹생리염수후4 h시,복강주사납락동4 mg/kg유발마배계단.급여납락동후30 min내관찰계단반응,병진행평분.계산대서체중변화폭도.급여납락동후1 h시처사대서,측정해마NR1、NR2A화NR2B적mRNA표체수평.결과 여C조비교,MD조、AO조화SO조계단반응평분화체중변화폭도승고,MD조화SO조해마조직NR2B mRNA표체상조(P<0.05혹0.01);여MD조비교,AO조계단반응평분화체중변화폭도강저,해마조직NR2A mBNA표체상조,NR2B mRNA표체하조(P<0.05혹0.01),SO조각지표차이무통계학의의(P>0.05).각조해마조직NR1 mRNA표체비교차이무통계학의의(P>0.05).결론 초내주사NR2B반의과핵감산가억제납락동유발마배의뢰대서계단반응,기궤제여해마NMDA수체아기수평화구성적변화조절유관.
Objective To investigate the effect of NR2B antisense oligonucleotide on naloxone-induced withdrawal responses in morphine-dependent rats. Methods Famale SD rats weighing 230-270 g were anesthetized with intraperitoneal pentobarhital 60 mg/kg. Intrathecal (IT)catheter was placed at L3,4 interspace.Thirty-two rats in which FT catheter was successfully placed were randomly divided into 4 groups ( n = 8 each) : group C control; group MD morphine dependence; group AO NR2B antisense oligonucleotide (aNR2B) and group SO NR2B sense oligonucleotide (sNR2B) . In group MD, AO, SO chronic morphine dependence was induced by increasing doses of subcutaneous morphine for 6 days. The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg twice every other day and reached 50 mg/kg on the 6th day. In group AO and SO IT aNR2B or sNR2B 15 nmol was administered simultaneously with subcutaneous morphine. Morphine withdrawal responses was induced by IT naloxone 4 mg/kg and scored based on the responses (0 = normal; higher scores signify severer responses) . The weight loss was calculated.The expression of NR1, NR2A and NR2B mRNA in hippocampus was determined by RT-PCR. Results The morphine withdrawal syndrome and weight loss were significantly incresed in group MD, AO and SO, while NR2B mRNA expression in hippocampus was up-regulated in group MD and SO compared with group C. The morphine withdrawal syndrome and weight loss were significantly decreased, NR2A mRNA expression in hippocampus was up-regulated and NR2B mRNA expression was down-regulated in group AO compared with group MD. There was no significant difference in NR1 mRNA expression between the 4 groups . Conclusion NR2B antisense oligonucleotide can suppress morphine withdrawal responses through the regulation of NMDA receptor level and construction in hippocampus.
