Protective effects and mechanisms of diammonium glycyrrhizinate on cognition dysfunction in rats with chronic cerebral hypoperfusion / 中华行为医学与脑科学杂志

ABSTRACT

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·kg -1·d -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. 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 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 ( P<0.05, 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) ( P<0.01), while the time of 2VO+ DAG group was shorter than that of 2VO group (14.26±1.51)s ( 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 ( P<0.01), while the rats in the 2VO+ DAG group were significantly more than those in the 2VO group ( 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)) ( 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 ( 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)( P<0.01), while that of 2VO+ DAG group (1.42±0.10) was significantly lower than that of 2VO group ( 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) ( P<0.01), while that in 2VO+ DAG group was significantly higher than that in 2VO group ((9.23±1.65)/10 μm) ( P<0.01). 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.