缰核对促睡眠区视前区-下丘脑前部的调节作用

Regulatory effect of habenular nucleus on sleep-promoting preoptic anterior hypothalamus

目的:观察缰核损毁及催眠药唑吡坦对视前区-下丘脑前部(PO/AH)腺苷和5-羟色胺(5-HT)相关基因mRNA表达的影响,探讨缰核在PO/AH促睡眠调节中的作用。方法:以30只雄性Wistar大鼠为实验动物,直流电损毁缰核或灌胃给予催眠药唑吡坦建立缰核损毁大鼠(n=15)和唑吡坦处理大鼠(n=15)两种动物模型,随后随机将大鼠分为缰核假手术组(n=7)、缰核损毁组(n=8)、生理盐水对照组(n=7)和唑吡坦处理组(n=8)。采用逆转录聚合酶链反应(RT-PCR)方法检测各组大鼠PO/AH内腺苷和5-HT相关基因mRNA的表达水平。结果:与假手术组相比,缰核损毁组大鼠PO/AH内除腺苷激酶mRNA表达的水平轻微升高(P>0.05)外,腺苷A1受体及5-HT相关基因mRNA的表达水平均明显上调(P<0.05)。与生理盐水对照组相比,唑吡坦处理组大鼠PO/AH内的5-HT相关基因mRNA表达明显降低(P<0.05);腺苷激酶的表达虽下调但无显著性差异(P>0.05),而腺苷A1受体的表达仅呈现轻微的上调(P>0.05)。结论:缰核对PO/AH的促睡眠过程具有调节作用,并且是通过腺苷和5-HT途径在此过程中发挥其作用。

ObjectiveTo study the expressions of adenosine and serotonin（5-HT）-related genes in the preoptic anterior hypothalamus（PO/AH） of rats with habenular lesions and with zolpidem treatment and to explore the effect of the habenular nucleus in the sleep-promoting regulation of the PO/AH.Methods Both a rat model with habenular lesion and a hypnotic-treated rat model were established by passing a DC current or by infusing with zolpidem into the stomach and then the rats were divided randomly into habenular sham group,habenular lesion group,vehicle group and zolpidem group.The mRNA levels of adenosine and 5-HT-related genes were examined by RT-PCR in the PO/AH.Results Compared with sham group,only the mRNA expression level of adenosine kinase in the PO/AH had a little increase in habenular lesion group（P〉 0.05）.However,the expressions of adenosine A1 receptor and 5-HT-related genes（tryptophan hydroxylase and 5-HT2A receptor） were significantly up-regulated in the PO/AH of habenular lesion group（P〈 0.05）.Compared with vehicle group,the mRNA expression levels of 5-HT-related genes were obviously diminished in the PO/AH of zolpidem-treated rats.Adenosine kinase expression was not statistically decreased（P〉 0.05）,but adenosine A1 receptor expression just had slight up-regulation in zolpidem group（P〉 0.05）.Conclusion Habenular nucleus has a regulatory effect on the sleep-promoting PO/AH and its effect is performed by the pathways of adenosine and 5-HT in this process.