酸枣仁汤对PCPA失眠大鼠大脑皮质代谢型谷氨酸受体和受体后cAMP、PKA的干预作用

Effect of Suanzaoren Decoction on cAMP and PKA after Metabolic Glutamate Receptor and Receptor in the Cerebral Cortex of Pcpa Insomnia Rats

目的:探讨PCPA失眠大鼠皮质代谢型谷氨酸受体(mGluRs)和受体后cAMP、PKAmRNA表达的变化及酸枣仁汤(SZRD)的干预作用。方法:采用连续3d腹腔注射氯苯丙氨酸350 mg·kg^(-1)的方法建立失眠大鼠模型,动物按随机数字表法分为空白对照组、模型组、SZRD大、中、小剂量组、SZRD对照组、5-HTP组,采用实时荧光定量PCR法检测皮质组织mGluR1、2、7及cAMP、PKAmRNA表达的变化。结果:模型组mGluR1、2、7 mRNA表达量显著增加,PKA、cAMP mRNA表达量明显下降。SZRD大剂量组和中剂量组的mGluR1、2、7mRNA表达量下降,SZRD大剂量组的PKA、cAMP mRNA表达量明显上升。SZRD本身并不改变正常大鼠皮质mGluR1、2、7、cAMP及PKAmRNA的表达,5-HTP组能导致皮质mGluR1、2 mRNA表达量增加,cAMP、PKAmRNA表达量明显下降。结论:PCPA引致皮质组织mGluR1、2、7mRNA表达量增加,PKA、cAMP mRNA表达量下降,SZRD能对上述变化发生干预作用。

Objective： To explore the expression of metabotropic glutamate receptors（ mGluRs）,PKA,cAMP gene mRNA in the frontal cortex in PCPA induced insomnia rats and the intervention effects of Suanzaoren Decoction（ SZRD）.Methods： Animals were randomly assigned to a control group,PCPA group,SZRD high-dose group,SZRD moderate-dose group,SZRD low-dose group,SZRD control group,and 5-HTP group. Each group was intra-gastric administration of appropriate therapy for seven days,real-time fluorescence quantitative PCR（ RT-PCR） was used to assess of cortical tissues mGluR1,mGluR2,mGluR7,cAMP,PKA mRNA gene expression changes. Results： In the model group,the expression of mGlu1,mGlu2 and mGlu7 receptor gene mRNA were significantly increased compared with control group. In the high-and moderate-dose SRZD groups,mGlu1,mGlu2 and mGlu7 receptor gene mRNA expression levels declined significantly compared with the model group in a dose-dependent manner. PKA mRNA and cAMP mRNA expression in the model group was significantly decreased compared with the control group,PKA mRNA and cAMP mRNA expression in the high-dose SRZD group was increased significantly compared with model group. SRZD itself does not alter the normal rat cortex mGluR1,mGluR2,mGluR7,cAMP and PKA gene mRNA expression. In the 5-HTP group,cortical mGlu1,mGlu2 receptor gene mRNA expression was significant increased,cAMP and PKA mRNA expression was significantly decreased compared with the control group, but the mGlu7 receptor gene mRNA expression was not significantly changed.Conclusion： PCPA insomnia can lead to increase in the cortical tissue mGlu1,mGlu2 and mGlu7 receptor gene mRNA expression,and decrease in PKA mRNA and cAMP mRNA expression. Suanzaoren decoction administration can mediate the effects of PCPA insomnia rats cortical mGlu1,mGlu2 and mGlu7 receptor gene mRNA expression levels,and change the post-receptor signal cAMP and PKA gene mRNA expression levels. This suggests that Suanzaoren decoction may be an effective treatment for insomnia,and the changes to mRNA expression may be the central mechanism of its effect.