杨静雯　林丽婷　李天然

摘要：目的 觀察针刺对血管性痴呆大鼠前额叶皮层Toll样受体4（TLR4）表达及下游炎症因子白细胞介素（IL）-1β和IL-6表达的影响，探讨针刺的脑保护作用。方法 50只大鼠随机分为假手术组、模型组、针刺组和非穴组。采用双侧颈总动脉永久性结扎方法制作血管性痴呆大鼠模型。造模后第3日针刺干预，每日1次，共2周。采用Morris水迷宫实验评价大鼠空间学习记忆能力，免疫组化检测小胶质细胞标志物离子钙结合蛋白1（Iba1）及TLR4表达，RT-PCR检测炎症因子IL-1β和IL-6的mRNA表达。结果 与假手术组比较，模型组大鼠空间学习记忆能力降低，前额叶皮层Iba1、TLR4及IL-1β、IL-6表达升高；与模型组比较，针刺组大鼠空间学习记忆能力改善，前额叶皮层Iba1、TLR4及IL-1β、IL-6表达降低；非穴组无明显改善。结论 针刺可抑制血管性痴呆大鼠前额叶皮质小胶质细胞激活，降低TLR4及其下游炎症因子表达水平，改善大鼠空间学习记忆能力。

关键词：血管性痴呆；针刺；小胶质细胞；Toll样受体4；炎症反应；大鼠

DOI：10.3969/j.issn.1005-5304.2018.06.012

中图分类号：R245 文献标识码：A 文章编号：1005-5304（2018）06-0048-05

Effects of Acupuncture on Inflammation in Prefrontal Cortex of Vascular Dementia Rats

YANG Jing-wen1， LIN Li-ting1， LI Tian-ran1， ZHANG Shuai1， WANG Xue-rui1， LIU Cun-zhi2

1. Beijing Hospital of TCM Affiliated to Capital Medical University， Beijing 100010， China；

2. Dongfang Hospital， Beijing University of Chinese Medicine， Beijing 100078， China

Abstract： Objective To observe the effects of acupuncture on TLR4， inflammation factors IL-1β and IL-6 expressions in the prefrontal cortex of vascular dementia （VD） rats； To investigate the brain protective mechanisms of acupuncture. Methods A total of 50 rats were randomly divided into sham-operation group， model group， acupuncture group， and placebo-acupuncture group. The animal model of VD was replicated by permanent bilateral common carotid artery occlusion （2VO） in rats. Acupuncture was performed at three days after surgery， once daily for two weeks. Morris water maze was used to test the cognitive function. The expressions of Iba1 and TLR4 were assessed by immunohistochemical method. Inflammation factors IL-1β and IL-6 mRNA expressions were tested by RT-PCR. Results Compared with sham-operation group， the model group rats showed impaired spatial learning and memory ability， and expression of Iba1， TLR4， and IL-1β， IL-6 increased. Compared with the model group， the spatial learning and memory abilities of the acupuncture group were improved， and the expression of Iba1， TLR4 and IL-1β， IL-6 in the prefrontal cortex decreased. These effects were not found in the placebo-acupuncture group. Conclusion The effect of acupuncture may be achieved by inhibiting microglia activate， decreasing the expressions of TLR4， IL-1β and IL-6 in the prefrontal cortex， resulting in improving spatial learning and memory ability of VD rats.

Keywords： vascular dementia； acupuncture； microgila； TLR4； inflammation； rats

血管性痴呆（vascular dementia，VD）是指各种脑血管疾病引起的大脑功能障碍而产生的一种慢性进行性获得性认知功能损害综合征。研究表明，炎症反应在慢性脑缺血后继发性神经损伤中起重要作用[1-2]。小胶质细胞是中枢神经系统中炎症发生的主要细胞，在免疫应答过程中起关键作用。Toll样受体（TLRs）是一组典型的内源性免疫反应的识别受体，国外研究显示，TLRs家族参与了神经炎症及痴呆的进程，Toll样受体4（TLR4）介导了脑缺血炎性损伤[3]。……