神经元型一氧化氮合酶反义寡脱氧核苷酸抑制大鼠吗啡戒断症状  

Neuronal nitric oxide synthase antisense oligodeoxynuleotide attenuates morphine withdrawal symptoms in rats

作　　者：周文华[1] 刘惠芬[1] 顾钧[1] 谢小虎[1] 唐甩恩[1] 杨国栋[1] 

机构地区：[1]宁波微循环与莨菪类药研究所.宁波戒毒研究中心,宁波315010

出　　处：《中国药理学通报》2000年第6期688-692,共5页Chinese Pharmacological Bulletin

基　　金：浙江省青年人才基金!资助课题;No 96 0 13;宁波市青年人才基金

摘　　要：目的　观察鞘内或侧脑室注射神经元型一氧化氮合酶 (nNOS)反义寡脱氧核苷酸对大鼠吗啡戒断症状的影响。方法　根据基因结构设计nNOS或eNOS反义寡脱氧核苷酸片段 ,用逆转录聚合酶链反应 (RT PCR)测定nNOSmR NA表达。结果　吗啡依赖大鼠在纳洛酮激发前 2 4h鞘内注射nNOS反义寡脱氧核苷酸抑制所有大鼠吗啡戒断症状如湿狗摇动、扭体及激惹、腹泻、体重减少、咬牙和流涎。eNOS反义寡脱氧核苷酸对吗啡戒断症状总评分值没有影响 ,但减少腹泻、体重减轻值和咬牙等评分值。侧脑室注射nNOS反义寡脱氧核苷酸减少吗啡戒断症状 ,eNOS反义寡脱氧核苷酸对吗啡戒断症状没有影响。鞘内注射nNOS反义寡脱氧核苷酸后脊髓nNOSmRNA的相对表达几乎消失 ,iNOS的表达增加 ;而eNOS反义寡脱氧核苷酸处理后对nNOS和iNOS的表达没有影响。结论　nNOS基因表达介导了吗啡戒断反应过程 ,抑制nNOS基因表达可增加脊髓i NOS基因的表达。AIM To characterize the role of neuronal nitric oxide synthase (nNOS) in morphine dependence process in rats. METHOD The specific antisense oligodeoxynucleotide (A olig) targeting nNOS and endothelial NOS (eNOS) were designed according to these gene structures, and nNOS, eNOS and inducible NOS (iNOS) mRNA levels were determined by using the reverse transcription polymerase chain reaction (RT PCR) method. RESULTS The intrathecal treatment with nNOS A olig (0 6 nmol per rat) at 24 h prior to naloxone challenge could block the morphine withdrawal symptoms including wet dog shaking, irritating, salivation, diarrhea, chewing and weight loss. A olig for eNOS (0 6 nmol per rat, it) only prevented the diarrhea and weight loss. The total ratings of morphine withdrawal symptoms as well as diarrhea and weight loss were attenuated by intraventricular (icv) nNOS A olig, however, icv A olig targeting eNOS, sense or mismatch oligodeoxynucleotide (it or icv) for nNOS was inactive. The iNOS mRNA expression, which has been found to exist in spinal cord, were increased and de creased during morphine dependence and withdrawal respectively. Moreover, nNOS mRNA levels were down regulated by intrathecal nNOS A olig, meanwhile, the iNOS mRNA levels in spinal cord were increased. CONCLUSION The results suggest that nNOS in spinal cord plays an important role in the expression of morphine withdrawal symptoms, and regulate the iNOS expression in spinal cord during morphine dependence.

关 键 词：阿片依赖 一氧化氮合酶 吗啡戒断症状 MRNA 

分 类 号：R971.2[医药卫生—药品] R595.6[医药卫生—药学]