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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。
Objective To observe the effects of intrathecal or intracerebroventricular injection of neuronal nitric oxide synthase (nNOS) antisense oligodeoxynucleotides on morphine withdrawal symptoms in rats. Methods The nNOS or eNOS antisense oligodeoxynucleotides were designed according to the gene structure. The nNOS mRNA expression was detected by reverse transcriptase polymerase chain reaction (RT PCR). Results Intrathecal injection of nNOS antisense oligodeoxynucleotides intrathecally in morphine-dependent rats at 24 hours prior to naloxone administration suppressed all morphine withdrawal symptoms such as wet dog shaking, writhing and irritation, diarrhea, weight loss, Drooling eNOS antisense oligodeoxynucleotides had no effect on the total score of morphine withdrawal symptoms, but decreased scores such as diarrhea, weight loss and teething. Intracerebroventricular injection of nNOS antisense oligodeoxynucleotide reduced morphine withdrawal symptoms, eNOS antisense oligodeoxynucleotides had no effect on morphine withdrawal symptoms. After intrathecal injection of nNOS antisense oligodeoxynucleotides, the relative expression of nNOS mRNA in spinal cord almost disappeared and the expression of iNOS increased. However, eNOS antisense oligodeoxynucleotide treatment had no effect on the expression of nNOS and iNOS. Conclusions nNOS gene expression mediates the morphine withdrawal reaction, and inhibition of nNOS gene expression can increase iNOS gene expression in the spinal cord.