目的 探索川芎挥发油对脂多糖（LPS）引起小鼠血管性认知障碍（VCI）的作用及其相关机制。方法 雄性C57BL/C小鼠随机分为假手术组、模型组、美金刚（10 mg/kg）组及川芎挥发油高、中、低剂量（30、15、7.5 mg/kg）组，每天ig给药1次，连续给药14 d，于第8天单侧icv LPS，第11天及第12天分别进行Y迷宫与跳台实验；末次给药后24 h断头处死小鼠，取脑组织测定其中单胺氧化酶（MAO）、乙酰胆碱酯酶（AchE）、乙酰胆碱（Ach）水平；同时体外考察药物对电鳗AchE、大鼠脑线粒体中超氧化物歧化酶（SOD）的直接作用和对LPS损伤的小鼠小胶质瘤BV-2细胞的作用。结果 与假手术组比较，模型组小鼠脑内MAO和AchE水平显著升高，多巴胺（DA）、5-羟色胺（5-HT）、去甲肾上腺素（NE）水平均显著降低；川芎挥发油高、中剂量均能显著降低VCI小鼠脑内MAO水平，各剂量均能显著降低VCI小鼠脑内AchE水平；行为学实验结果显示川芎挥发油各剂量均能够显著增加VCI小鼠的在Y迷宫实验中自发交替反应次数，川芎挥发油中剂量能显著降低VCI小鼠在跳台实验中的潜伏期。体外实验发现，川芎挥发油质量浓度为1 mg/mL时对电鳗AchE有微弱的抑制作用；川芎挥发油0.5 μg/mL能显著抑制BV-2细胞肿瘤坏死因子-α（TNF-α）和NO水平的升高。结论 川芎挥发油能够明显改善LPS致VCI小鼠的认知能力，其机制可能与抑制脑内炎症反应、减轻对神经元损伤有关。

Objective To explore the effect of volatile oil of Ligusticum chuanxiong on vascular cognitive impairment (VCI) induced by lipopolysaccharide (LPS) and its related mechanism.Methods Male C57BL/C mice were randomly divided into sham-operated group, model group, memantine (10 mg/kg) group, and volatile oil of L. chuanxiong (30, 15, and 7.5 mg/kg) groups, drugs were given by ig administration once a day for 14 d. On day 8, LPS was injected into the lateral ventricle in mice. On day 11 and day 12, the cognitive ability were checked by the Y maze and step down test. On day 15 the mice were decapitated and the brain tissue was taken to determine the levels of monoamine oxidase (MAO), acetylcholinesterase (AchE), and acetylcholine (Ach); At the same time, the effect of the drug on superoxide dismutase (SOD) in mitochondria of brain in SD rats and the activity of Ec AchE, and BV-2 cells of microgliomas injured by LPS were also investigated in vitro.Results LPS significantly increased the levels of MAO and AchE in the brain in mice, while decreased the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE). The volatile oil of L. chuanxiong 30 or 15 mg/kg decreased the level of MAO and AchE in the brain of LPS mice. The volatile oil of L. Chuanxiong could significantly increase the times of spontaneous alternation reaction in Y maze in VCI mice, and the middle dose could significantly decrease the latency of VCI mice in step down test. In vitro, the volatile oil of L. chuanxiong 1 mg/mL had a weak inhibitory effect on AchE of electric eel. The volatile oil of L. chuanxiong 0.5 μg/mL could significantly increase the activity of SOD in brain mitochondria of rats, and decrease the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) increased significantly in BV-2 cells induced by LPS. Conclusion The volatile oil of L. chuanxiong can significantly improve the cognitive ability of VCI induced by LPS in mice, and its mechanism may be related to inhibit the inflammatory response in the brain and alleviate the injury of neurons.

R285.5

四川省科技厅成果转化项目（2018YSZH0012）；成都市科技局科技惠民技术研发项目（2016-HM01-00378-SF）