酸枣仁汤对GABAB1R介导快动眼睡眠剥夺老年大鼠下丘脑室旁核cAMP-PKA-CREB信号通路的影响  

Effects of Suanzaoren Decoction on cAMP- PKA- CREB Signaling Pathway in Hypothalamic Paraventricular Nuclear( PVN) Mediated by GABAB1R in Aged rat with REM Sleep Deprivation

作　　者：游秋云[1] 王平 张舜波 黄攀攀 章程鹏 

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]国家中医药管理局老年性痴呆醒脑益智重点研究室

出　　处：《世界睡眠医学杂志》2014年第3期129-134,共6页World Journal of Sleep Medicine

基　　金：国家自然科学基金(编号:81072849)

摘　　要：目的观察酸枣仁汤对快动眼睡眠被剥夺老年大鼠下丘脑室旁核(PVN)cAMP-PKA-CREB信号通路的影响。方法将自然衰老24月龄Wistar大鼠随机分成空白对照组(等容生理盐水),老年REM睡眠剥夺组(等容生理盐水),阳性对照组(舒乐安定0.18 mg/(kg·d),酸枣仁汤低、高剂量组(12.96、25.92 g/(kg·d)。各组灌胃给药2周后,除空白对照组外其余各组用自制改良多平台法剥夺大鼠睡眠48 h制作老年大鼠REM睡眠剥夺模型。采用免疫组化方法检测大鼠PVN内GABAB1R阳性反应物的变化;采用酶联免疫法和免疫组织化学法检测PVN部位环腺苷酸(cAMP)和磷酸化cAMP反应元件结合蛋白(CREB)水平变化,检测PVN匀浆液中磷酸二酯酶(PDE)活性的变化。结果与空白对照组比较,老年REM睡眠剥夺组大鼠PVN部位的GABAB1 R阳性反应物数目明显增多(P<0.01),cAMP和p-CREB水平均明显降低,PDE活性明显增高(P<0.01);与老年REM睡眠剥夺组比较,酸枣仁汤低、高剂量组大鼠PVN部位的GABAB1 R阳性反应物数目明显减少(P<0.01),cAMP和p-CREB水平均明显提高,PDE活性明显降低(P<0.01)。结论实验结果表明,酸枣仁汤可能通过增强GABAB1 R表达来激活cAMP-PKA-CREB信号通路而发挥安神健脑作用。Objective Observe the effect of Suanzao-Rentang on cAMP-PKA-CREB signaling pathway in hypothalamic paraventricular nuclear（PVN）ofaged rat whose rapid eye movement sleep has been deprived.Methods Natural age24 month-old Wistar rats arerandomly divided into control group（isovolumetric saline）,REM sleep deprivation elderly group（isovolumetric saline）,positive control group（estazolam 0.18 mg/（kg·d）,Suanzao-Rentang low and high dose group（12.96,25.92 g/（kg·d）.Each group isgiven intragastric administration for two weeks.After that,except for the control group,each group is made REM sleep deprivation 48hours production model of old rats with homemade improved multi-platform.Then,we use Immunohistochemistry for detecting changes of GABAB1R positive reactant in the rat PVN,enzyme-linked immunosorbent assay and immunohistochemistry for detecting changes of cyclic adenosine monophosphate（cAMP）in part of PVN and cAMP response element binding protein（CREB）levels,as well as activity of homogenate phosphodiesterase（PDE）in PVN.Results Compared with the control group,the amountof positive reaction GABAB1 R in PVN sitessignificantly increases（P〈0.01）, cAMP and p-CREB levels significantly reduce,PDE activity significantly increases（P〈0.01）in the REM sleep deprivation old＆amp;nbsp;rats;compared with the older group in which the ratesREM sleep hasbeen deprived,the positive reaction amountof GABAB1 R in PVN significantly reduces（P〈0.01 ）,cAMPbutp-CREB levels significantly increases,PDE activity significantly reduces（P〈0.01）in Suanzao-Rentang low and high-dose group of rats.Conclusion The results show that Suanzao-Rentang possibly play a role in brain nerves by enhancing GABAB1 R expression whichactivates cAMP-PKA-CREB signaling pathway.

关 键 词：老年失眠 酸枣仁汤 大鼠模型机制 

分 类 号：R338[医药卫生—人体生理学]