电针防治老龄大鼠POCD的海马神经免疫调节机制研究

Postoperative cognitive dysfunction(POCD) is frequent in elderly patients after surgery. POCD gravely influence the quality of life and can't be effectively treated and prevented. The exact mechanism has not been clarified. Recently, some scientists consider that POCD may relative to the postoperative hippocampus inflammation. As is known to all, hippocampus plays an important role in cognition. However, the relationship between POCD and postoperative hippocampus injury has not been exactly reported up to now. Through clinical practices, we found that the use of electricity-acupuncture before and after operation could relieve symptom. In addition, it has been already confirmed that electricity-acupuncture could inhibit hippocampus inflammation, restrain neurons apoptosis, boost neurogenesis and improve cognitive function after rat cerebral ischemia. The hypothetic basic pathology of POCD is the stress reaction after surgery stimulates microglia activity which caused by aging brain due to induce inflammatory cascade reaction and further led to injure hippocampus neurons and inhibit neurogenesis. To prove this hypothesis, we plan to make some aging rat models, then search the exactly pathology mechanism of POCD through using new technology of molecular biotechnology, pathology, morphology and neuroethology. Base on the new discovery, we hope we can find that electricity-acupuncture how to treat and prevent POCD and inhibit hippocampus inflammation. Thereby, we can make a contribution to determinate effective therapeutic methods and expand the range of acupuncture treatment.

术后认知功能障碍（POCD）多发于老年受术者，严重影响其生存质量，至今尚无有效的防治方法。其确切机制尚未阐明，近期多认为与术后引发的海马炎症反应有关。公认海马是记忆形成的关键脑区。但老龄人群术后海马神经元易损性的病理基础及其与POCD发生发展的相关性，迄今国内外未见报道。我们近期临床发现，围手术期电针可有效减轻POCD症状；且证实电针可抑制大鼠脑缺血后海马炎症反应与神经元凋亡、促进神经发生，改善记忆能力。推测手术创伤及应激刺激脑老化所致敏的小胶质细胞活化导致炎性级联反应，造成海马神经元和神经发生的损害可能是POCD发生的病理基础。为证实假说，我们将复制老龄大鼠POCD模型，采用分子生物、病理形态及神经行为学等技术，从分子-细胞-行为三个层次，以新的视角揭示其发生的病理机制，并探寻电针防治POCD的作用规律及抑制海马炎症反应的作用机制，为开拓有效防治方法、扩大针灸治疗适应范围作出积极的贡献。

术后认知功能障碍（POCD）多发于老年受术者，严重影响其生存质量，至今尚无有效的防治方法。其确切机制尚未阐明，近期多认为与术后引发的海马炎症反应有关。但老龄人群术后海马神经元易损性的病理基础及其与POCD 发生发展的相关性，迄今尚未明确。.我们选择老龄大鼠为主复制POCD 模型，采用分子生物、病理形态及神经行为学等技术，从分子-细胞-行为三个层次揭示其发生的病理机制，并探寻电针防治POCD 的作用规律。研究证实年龄依赖性的中枢神经元-胶质细胞交互作用（cross-talk）失衡致使胶质细胞处于一种致敏（primed/sensitized）状态；以及中枢内外年龄依赖性的HPA轴活动增强，低强度的炎症反应、氧化应激状态及RAS系统的活化趋势，构成了老龄POCD易发性的病理基础。在手术创伤刺激下，加剧应激反应、外周免疫攻击、RAS系统活化，导致海马炎症反应、氧化应激损伤，而诱导POCD的发生、发展。电针干预及电针预处理对老龄POCD可起到有效的防治作用，其作用机制可能在于调节中枢神经元-胶质细胞的交互作用，抑制胶质细胞活化，抑制炎症反应、降低氧化应激，改善POCD症状。本研究开拓了有效防治POCD 的新方法，扩大针灸治疗适应范围；并为临床开展相应的研究与治疗提供了有针对性的作用靶点。