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目的:探讨甘草酸二铵(diammonium glycyrrhizinate，DAG)对慢性脑低灌注所致认知功能障碍中的保护作用和机制。方法:73只雄性SPF Sprague Dawley (SD)大鼠，分为假手术组(sham组)、慢性脑低灌注组(2VO组)、脑低灌注甘草酸二铵治疗组(2VO＋DAG组)和甘草酸二铵治疗组(DAG组)，采用双侧结扎颈总动脉方法建立慢性脑低灌注模型，期间腹腔注射2.917 mmol/L DAG(20 mg·kgn －1·dn －1)或等量生理盐水15 d。利用Morris水迷宫、Elisa、蛋白免疫印迹和Golgi染色方法，分别检测大鼠的空间学习记忆能力、海马组织炎症因子水平和炎症信号通路分子的变化，并观察树突棘的分布水平。n 结果:Morris水迷宫测试显示在训练第3～7天2VO组大鼠学习潜伏期[(50.70±2.01)s、(43.53±3.22)s、(35.41±2.13)s、(25.26±1.85)s、(17.92±2.24)s]明显长于sham组[(40.28±1.94)s、(31.51±3.23)s、(24.7±2.25)s、(13.23±2.51)s、(9.42±1.91)s] (均n P<0.01)，而2VO＋DAG组大鼠的学习潜伏期[(46.27±1.64)s、(38.54±1.51)s、(28.74±2.52)s、(19.73±2.13)s、(13.26±1.71)s]则显著短于2VO组(n P<0.05，n P<0.01)。撤掉平台检测大鼠记忆，也显示2VO大鼠到达平台潜伏期[(18.56±1.72)s) ]比假手术组显著长[(11.25±2.11)s](n P<0.01)，而2VO＋DAG组大鼠[(14.26±1.51)s]则较2VO组花费较短的时间达到原平台位置(n P<0.01)。同时在平台所在象限区域滞留时间和穿梭平台区域的次数方面，2VO组大鼠均显著少于sham组(n P<0.01)，而2VO＋DAG组大鼠均显著多于2VO组(n P<0.01)。Elisa法检测大鼠海马组织炎症因子，发现2VO组大鼠这三种炎症因子水平TNF-α、IL-1β和IL-6 [TNF-α：(27.42±1.91)pg/mg; IL-1β：(18.21±1.56)pg/mg; IL-6：(17.94±1.61)pg/mg)]均高于sham组[TNF-α：(8.11±1.27)pg/mg; IL-1β：(6.78±1.12)pg/mg; IL-6：(5.67±0.91)pg/mg)](n P<0.01)，而2VO＋DAG组的三种炎症因子水平[TNF-α：(12.25±2.38)pg/mg; IL-1β：(9.93±0.96)pg/mg; IL-6：(8.72±0.65)pg/mg)]均显著低于2VO组(n P<0.01)。蛋白免疫印迹结果显示，2VO组胞核里的NF-κB相对水平(1.82±0.15)显著高于sham组(1.00±0.09)(n P<0.01)，而2VO＋DAG组胞核NF-κB相对水平(1.42±0.10)显著低于2VO组(n P<0.01)。Golgi染色显示，2VO组海马CA1区神经元树突的树突棘密度[(5.00±1.41)个/10 μm]显著低于sham组[(12.86±1.12)个/10 μm](n P<0.01)，而2VO＋DAG组的树突棘密度[(9.23±1.65)个/10 μm]则显著高于2VO组(n P<0.01)。n 结论:甘草酸二胺能够有效通过抑制慢性脑低灌注海马的神经炎症反应，并改善突触可塑性的损伤，进而能够改善慢性低灌注引起的认知功能障碍。甘草酸二胺可作为潜在的治疗慢性脑缺血所致认知功能障碍乃至血管性痴呆的有效药物。“,”Objective:To explore the protective effect and mechanism of diammonium glycyrrhizinate (DAG) on cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Seventy-three male Sprague Dawley rats in SPF degree were divided into sham group, chronic cerebral hypoperfusion group(2VO group), chronic cerebral hypoperfusion with DAG treatment group(2VO+ DAG group), and DAG treatment group(DAG group). During one-month chronic cerebral hypoperfusion models reproduced by the occlusion of bilateral common caroid artery, the rats were injected intraperitoneally with 2.917 mmol/L(20 mg·kgn -1·dn -1) DAG or saline for 15 days.Then the ability of learning and memory were tested by Morris water maze.Elisa, Western blot and Golgi staining were employed to test the spatial cognition, the changes of inflammatory factors, and inflammatory signal pathway molecules in hippocampus.The distribution of dendritic spines were observed and counted.n Results:Morris water maze test showed that the learning latency of rats in 2VO group (3rd -7th day ) ((50.70±2.01)s, (43.53±3.22)s, (35.41±2.13)s, (25.26±1.85)s, (17.92±2.24)s) was significantly longer than that of sham group((40.28±1.94)s, (31.51±3.23)s, (24.7±2.25)s, (13.23±2.51)s, (9.42±1.91)s) (all n P<0.01), while that of 2VO+ DAG group ((46.27±1.64)s, (38.54±1.51)s, (28.74±2.52)s, (19.73±2.13)s, (13.26±1.71)s) was significantly shorter than that of 2VO group (n P<0.05,n P<0.01). After removing the platform to detect the memory of rats, the results showed that the latency of 2VO group (18.56±1.72)s) was significantly longer than that of sham operation group (11.25±2.11)s) (n P<0.01), while the time of 2VO+ DAG group was shorter than that of 2VO group (14.26±1.51)s (n P<0.01). In terms of the time of staying in the platform quadrant, the times of crossing through the platform area, the rats in the 2VO group were significantly less than those in the sham group (n P<0.01), while the rats in the 2VO+ DAG group were significantly more than those in the 2VO group (n P<0.01). Elisa data showed the levels of TNF-α, IL-1β and IL-6 in 2VO group (TNF-α: (27.42±1.91) pg/mg; IL-1β: (18.21±1.56)pg/mg; IL-6: (17.94±1.61)pg/mg)) were higher than those in sham group (TNF-α: (8.11±1.27)pg/mg; IL-1β: (6.78±1.12)pg/mg; IL-6: (5.67±0.91)pg/mg)) (n P<0.01), while the levels of three inflammatory factors in 2VO+ DAG group (TNF-α: (12.25±2.38)pg/mg; IL-1β: (9.93±0.96)pg/mg; IL-6: (8.72±0.65)pg/mg)) were significantly lower than those in 2VO group (n P<0.01). Western blotting data showed that the relative level of NF-κB in the nucleus of 2VO group (1.82±0.15) was significantly higher than that of sham group (1.00±0.09)(n P<0.01), while that of 2VO+ DAG group (1.42±0.10) was significantly lower than that of 2VO group (n P<0.01). Golgi staining showed that the density of dendritic spines in CA1 area of hippocampus in 2VO group ((5.00±1.41)/10 μm) was significantly lower than that in sham group ((12.86±1.12)/10 μm) (n P<0.01), while that in 2VO+ DAG group was significantly higher than that in 2VO group ((9.23±1.65)/10 μm) (n P<0.01).n Conclusion:DAG can effectively inhibit the neuroinflammatory response of hippocampus in chronic cerebral hypoperfusion, improve the damage of synaptic plasticity, and then improve the cognitive dysfunction caused by chronic hypoperfusion.DAG may be a potential effective drug for the treatment of chronic cerebral ischemia and vascular dementia.