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Objective To explore the role of interleukin-18 binding protein (IL-18BP) in alleviating cognitive dysfunction of traumatic brain injury (TBI) rats and the related mechanisms. Methods A total of 120 adult male SD rats were randomly divided into 4 groups (30 each): sham group, TBI group, TBI+IL-18BP group (administered 1.5 mg/kg IL-18BP by tail vein), and TBI+IL-18BP+ADU-S100 group (administered 1.5 mg/kg IL-18BP by tail vein, and 20 mg/kg ADU-S100 by intraperitoneal injection). The rat model of TBI was established using the free falling body method. At 30 d after modeling, cognitive function of rats was measured by Morris water maze test. The serum levels of IL-18 and IL-18BP were detected by ELISA. The integrated fluorescence intensity of GFAP, IL-18 and cleaved-caspase-3 in hippocampus were detected by immunofluorescence. The relative expression levels of stimulator of interferon genes (STING), phosphorylated TANK-binding kinase 1 (p-TBK1), TBK1, phosphorylated interferon regulating factor 3 (p-IRF3), and IRF3 in hippocampus were detected using Western blotting. Results Compared with sham group, rats in TBI, TBI+IL-18BP and TBI+IL-18BP+ADU-S100 groups had longer escape latency and decreased times of crossing the platform and reduced time of acting in the targeted quadrant (P<0.0001), with increased concentration of IL-18 and IL-18BP in the blood, enhanced fluorescence intensity of IL-18 and cleaved-caspase-3, up-regulated expression levels of STING, p-TBK1 and p-IRF3 in the hippocampus (P<0.05); Compared with TBI group, the escape latency was shortened, the times of crossing platform and the percentage of target quadrant activity time were increased in TBI+IL-18BP group (P<0.001), the concentration of serum IL-18 decreased while of serum IL-18BP increased, and the fluorescence intensity of IL-18 and cleaved-caspase-3, the expressions of STING, p-TBK1 and p-IRF3 in the hippocampus were down-regulated significantly in TBI+IL-18BP group (P<0.05); Compared with TBI+IL-18BP group, the latency was significantly prolonged, the platform crossing times remarkably reduced, the time spent in the target quadrant was considerably shortened, the concentration of serum IL-18 increased while of IL-18BP decreased, the fluorescence intensity of IL-18 and cleaved-caspase-3, the expression levels of STING, p-TBK1 and p-IRF3 in hippocampus were increased in TBI+IL-18BP+ADU-S100 group (P<0.05). Conclusion IL-18BP can improve the cognitive function of TBI rats to some extent, and its mechanism may be related to the inhibition of astrocytes apoptosis and STING/TBK1/IRF3 signaling pathway.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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