目的:观察吗啡戒断大鼠侧脑室胶质细胞源性神经营养因子(glial cell derived neurotrophic factor,GDNF)反义寡脱氧核苷酸注射后对海马GDNFmRNA表达的影响。方法:SD大鼠侧脑室立体定位,皮下注射吗啡建立吗啡依赖大鼠模型,侧脑室微注射GDNF有义和反义寡脱氧核苷酸,纳洛酮催促戒断,应用原位杂交方法检测海马GDNFmRNA的表达。结果:侧脑室注射GDNF反义寡脱氧核苷酸能显著抑制大鼠吗啡戒断症状评分(n=t,p〈0.05)。吗啡依赖大鼠海马CA2区GDNFmRNA表达较对照组显著增加(n=3,P〈0.05),CA1和CA3区变化不明显;吗啡依赖大鼠纳洛酮(4mg/kg,岫催促戒断后海马CA1、CA2和CA3区GDNFmRNA表达较依赖组有增加趋势,但均没有显著差异心=3,P〉0.05);吗啡依赖大鼠纳洛酮激发前24h侧脑室注射GDNF反义寡脱氧核苷酸能显著抑制吗啡依赖大鼠依赖和戒断后CA2区GDNFmRNA表达的增加(n=3,p〈0.05),而CA1和CA3区与戒断组大鼠相应区域相比没有差异;吗啡依赖大鼠纳洛酮激发前24h侧脑室注射GDNF有义寡脱氧核苷酸与戒断组大鼠相比海马CA1、CA2和CA3区GDNFmRNA表达均没有显著性差异(n=3,P〉0.05)。结论:在转录水平,海马CA2区GDNF表达的变化在吗啡依赖和戒断中可能起重要作用。
Objective: To observe the GDNF mRNA expression in hippocampus ofmorphine-withdarwal rats after microinjecting glial cell derived neurotrophic factor(GDNF) antisense oligonucleotide into lateral ventricle. methods: SD rats were established morphine dependence rats model, microinjecting GDNF antisense and sense oligonucleotides were injected into rats lateral ventricle, then detecting the GDNF mRNA expression of hippocampus by in situ hybridization. Results: Injection GDNF antisense oligonucleotides into lateral ventricle decreased the scores of morphine withdrawal syndrome. The expression of GDNF mRNA in hippocampus CA2 zone increased in morphine dependence and withdrawal rats.The upreguluted expression of GDNF mRNA in hippocampus CA2 zone could be inhibited by microinjection GDNF antisense oligonucleotide into lateral ventricle.In contrast, microinjection GDNF sense oligonucleotide did not block the expression of GDNF mRNA in hippocampus CA2 zone of morphine withdrawal rats. Conclusion: The results suggest that the expression of GDNF mRNA in hippocampus CA2 zone plays a important role in morphine dependence and withdrawal on transcription level.