酸枣仁汤对基于5-HTR调控老年失眠SCN及VLPO系统的作用及机制研究

Studies have shown that the function of the hypothalamic suprachiasmatic nucleus (SCN) and it's regulation system named the hypothalamus ventrolateral preoptic area (VLPO) reducing may be the main cause of the elderly of sleep circadian and activity rhythms' gradually decay and broken. This paper intends to further investigate the role and mechanism of Spine Date Seed Decoction(SDSD) for SCN system and VLPO projection systems in senile insomnia and their relationship . This paper intends to make aged rats chronic rapid eye movement sleep deprivation naturally aged 24-month-old Wistar rats with the way of multi-platform environment Water which has been internationally recognized. Then it explore not only the role and mechanism of SDSD for elderly insomnia at the lever of 5-HTR in regulating SCN and VLPO system from the aspect of myocardial apoptosis genes ,brain ultrastructural pathology , neuronal activity , neuropeptides and neurotransmitters and related receptor expression and so on , but also the relevance between elderly insomnia and SCN system and VLPO system. Combine with the results of previous research on behavior and patholog, it comprehensive analysis the function mechanism of SDSD for improvement of myocardial apoptosis and brain damage. It is expected to provide experimental evidence for SDSD to prevent and treat senile insomnia and enrich and develop geriatric medicine and treatment as well as therapies theory.

有研究表明，衰老引起的下丘脑视交叉上核（SCN）及其调节系统下丘脑腹外侧视前区(VLPO)的功能退化降低可能是导致老年人的昼夜睡眠、活动节律逐渐衰减和破碎的主要原因。本课题拟探讨酸枣仁汤对老年失眠下丘脑视交叉上核（SCN）系统和下丘脑腹外侧视前区(VLPO)系统及两者投射关系的作用及机制研究。拟选用自然老年24月龄Wistar大鼠，采用国际上公认的多平台水环境法建立老年大鼠慢性快动眼睡眠剥夺模型，然后从心肌细胞凋亡基因、脑超微病理、神经元活性、神经肽和神经递质及其相关受体表达等方面，探讨酸枣仁汤对基于5-HTR调控老年失眠SCN及VLPO系统的作用及机制，以及老年失眠与SCN系统和VLPO系统的相关性。同时，结合前期行为学及病理等研究结果，综合分析酸枣仁汤对心肌细胞凋亡和脑损伤的改善作用机制。以期为酸枣仁汤防治老年失眠提供实验依据，并丰富和发展中医老年病及其治则治法理论。

中医药防治老年失眠症具有辨证施治、标本兼治、更安全有效的明显优势。“养血滋阴安神治法”对失眠尤其是老年失眠的疗效已为临床所证实，而东汉医家张仲景创立的酸枣仁汤就是最能代表该治法的经典名方。有研究表明，衰老引起的下丘脑视交叉上核（SCN）及其调节系统下丘脑腹外侧视前区(VLPO)的功能退化降低可能是导致老年人的昼夜睡眠、活动节律逐渐衰减和破碎的主要原因。已知SCN系统、VLPO系统在老年失眠中存在着重要的病理机制，而VLPO中的抑制性神经递质GABA、Gal对这两个系统的投射关系起到关键作用。另外，VLPO系统觉醒中枢上行激活通路中的5-HT，可参与多种行为、情绪活动及睡眠的调节。. 本课题探讨了酸枣仁汤对老年失眠下丘脑视交叉上核（SCN）系统和下丘脑腹外侧视前区(VLPO)系统及两者投射关系的作用及机制研究。选用自然老年24月龄Wistar大鼠，采用国际上公认的多平台水环境法剥夺睡眠48h，建立老年大鼠睡眠剥夺模型，从心肌细胞凋亡基因、脑超微病理、神经元活性、神经肽和神经递质及其相关受体表达等方面，探讨酸枣仁汤对基于5-HTR调控老年失眠SCN及VLPO系统的作用及机制，以及老年失眠与SCN系统和VLPO系统的相关性。研究结果表明，酸枣仁汤可减少老年慢性睡眠剥夺大鼠心肌细胞凋亡数目，降低心肌细胞bcl-2、bax蛋白表达；改善老年慢性睡眠剥夺大鼠SCN形态超微病理变化，下调SCN中nNos、c-fos mRNA表达，上调SCN中VIP、AVP mRNA表达；改善老年慢性睡眠剥夺大鼠VLPO神经细胞形态病理改变，上调下丘脑5-HT1AmRNA表达、下调5-HT2AmRNA表达，下调下丘脑GABAARα1及GABAARγ2 mRNA表达、增加下丘脑GABA、甘丙肽神经元表达、升高下丘脑5-HT含量。以上实验研究结果及前期研究基础表明，老年失眠与SCN系统和VLPO系统具有密切相关性，酸枣仁汤可基于5-HTR调控老年失眠SCN及VLPO系统，从而有效改善老年慢性失眠病理变化及睡眠。. 该项研究通过探索酸枣仁汤对心肌细胞凋亡和脑损伤的改善作用机制，为酸枣仁汤防治老年失眠提供了实验依据，并丰富和发展了中医老年病及其治则治法理论。