To explore the role and mechanism of glycyrrhizic acid, a high-migration group protein B1 (HMGB1) inhibitor, in cognitive disorders in rats with traumatic brain injury (TBI).

Thirty healthy and clean male rats were screened and divided into sham surgery group, model group and inhibitor group by random number table method, with 10 rats in each group. The model group and inhibitor group constructed a TBI cognitive disorder model through the strike method. After modeling, the inhibitor group was injected with glycyrrhizic acid (10 mg/kg) in the peritoneal cavity, once every 6 h for 4 times; the model group was injected with the same dose of physiological saline in the peritoneal cavity. The pseudo-operation group only routinely opened the skull, did not strike, and injected the abdominal cavity and other doses of physiological saline. Morris water maze experiment was used to screen rats with cognitive dysfunction; ELISA was used to detect the activity of total superoxide dismutase (SOD), malondialdehyde (MDA), and the expression levels of high mobility group protein B1 (HMGB1), Toll like receptor 4 (TLR4), and matrix metalloproteinase-9 (MMP9) in serum; Western blot was used to detect the expression of related proteins in brain tissue and hippocampus; RT-qPCR was used to detect the mRNA expression levels of MMP9, HMGB1, and TLR4.

(1) Water maze laboratory test. Positioning navigation experiment: The latency period of the model group was longer than that of the sham surgery group and the inhibitor group, and the difference was statistically significant (P<0.05). Space exploration experiment: Compared with the sham surgery group and the inhibitor group, the number of times they passed through the target quadrant, the distance from the target quadrant, and target quadrant time were all reduced, and the difference was statistically significant (P<0.05). (2) ELISA detection: Compared with the sham surgery group, the SOD activity of the model group rats decreased, while the MDA content and the expression levels of HMGB1, MMP9, and TLR4 increased; Compared with the model group, the inhibitor group showed SOD activity increased, MDA content and expression levels of HMGB1, MMP9, TLR4 decreased, and the differences were statistically significant (P<0.05). (3) RT-qPCR detection: The mRNA expression of MMP9, HMGB1, and TLR4 in the model group rats was higher than that in the sham operation group and inhibitor group, and the differences were statistically significant (P<0.05). (4) Western blot experiment: The expression levels of HMGB1, MMP9, and TLR4 proteins in the model group rats were higher than those in the sham operation group and inhibitor group, and the differences were statistically significant (P<0.05).

HMGB1 inhibitors can improve cognitive impairment in TBI rats, reduce the expression levels of MDA, MMP9, TLR4, and HMGB1, and enhance SOD activity.