Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF
Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF
复制标题
星形细胞磷脂酶A(2)-花生四烯酸通路的良性调节：手法针灸对CBF有益作用的潜在机制
DOI：
10.3389/fnins.2019.01354
复制
发表时间：
2020-02-04
影响因子：
4.3
通讯作者：
Li, Zhigang
中科院分区：
文献类型：
--
作者：
Ding, Ning;Jiang, Jing;Li, Zhigang
研究背景星形胶质细胞磷脂酶A（2）（PLA（2））-花生四烯酸（AA）通路在理解认知功能减退前脑血流量（CBF）减少的过程中起着至关重要的作用。在补充和替代医学中，手针（MA）被用作阿尔茨海默病（AD）最重要的治疗方法之一。MA对CBF的有益作用在我们以前的研究中已有报道。目的探讨MA对SAMP 8小鼠脑星形胶质细胞PLA 2-AA通路的影响。方法SAMP 8小鼠分为对照组（Pc）、MA组（Pm）和多奈哌齐组（Pd）。SAMR 1小鼠用作SAMR 1对照（Rc）组。Pd组小鼠用0.65 μ g/g盐酸多奈哌齐治疗。Pm组用MA贴敷百会、印堂20 min，1次/d，连续26 d。Morris水迷宫检测大鼠空间学习记忆能力。结果与Rc组相比，Pc组大鼠的逃避潜伏期明显延长（P < 0. 05），与Rc组相比，Pc组大鼠的逃避潜伏期延长（P < 0. 05），与Rc组相比，Pc组大鼠的逃避潜伏期延长（P < 0. 05），与Rc组相比，Pc组大鼠的逃避潜伏期延长（P < 0. 05而平台象限的跨平台次数、时间百分比和游泳距离百分比均减少（P < 0.01）。Pc组海马PLA（2）、COX-1、细胞色素P450蛋白2C 23的表达及AA、PGE 2、epoxyeicosatrienoic acids的含量均显著高于Rc组（p < 0.01）。结论MA能有效改善SAMP 8小鼠的学习记忆能力，并对PLA 2-AA通路有负调节作用。我们认为，动脉张力的增加，这是由血管舒张通路的抑制，可能是一个原因，对CBF的MA的有益效果。
BackgroundThe astrocytic phospholipase A(2) (PLA(2))-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer's disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive.ObjectiveTo investigate the effect of MA on the astrocytic PLA(2)-AA pathway in SAMP8 mice hippocampi.MethodsSAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 mu g/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory. Immunofluorescence staining, western blot and liquid chromatography-tandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA(2)-AA pathway.ResultsCompared with that in the Rc group, the escape latency in the Pc group significantly increased (p < 0.01); whereas, the platform crossover number and percentage of time and swimming distance in the platform quadrant decreased (p < 0.01). The hippocampal expression of PLA(2), cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E-2 and epoxyeicosatrienoic acids of the Pc group was drastically higher than that in the Rc group (p < 0.01). These changes were reversed by MA and donepezil (p < 0.01 or p < 0.05).ConclusionMA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA(2)-AA pathway. We propose that the increase of the arterial tone, which is induced by the inhibition of vasodilatory pathway, may be a reason for the beneficial effect of MA on CBF.