探讨高迁移率族蛋白B1（HMGB1）抑制剂甘草酸在创伤性颅脑损伤（TBI）大鼠认知障碍中的作用及机制。

筛选健康清洁雄性大鼠30只，采用随机数字表法分为假手术组、模型组及抑制剂组，每组10只。模型组与抑制剂组通过打击法构建TBI认知障碍模型。造模后，抑制剂组腹腔注射甘草酸（10 mg/kg），每6小时注射一次，持续4次；模型组腹腔注射等量生理盐水。假手术组仅常规开颅，不予打击，腹腔注射等量生理盐水。采用Morris水迷宫实验筛选存在认知障碍的大鼠；ELISA检测血清中总超氧化物歧化酶（SOD）活性、丙二醛（MDA）及高迁移率族蛋白B1（HMGB1）、Toll样受体4（TLR4）及基质金属蛋白酶9（MMP9）表达量；Western blot检测脑组织及海马中相关蛋白的表达；RT-qPCR检测MMP9、HMGB1、TLR4的mRNA表达量。

（1）水迷宫实验。定位航行实验：模型组的潜伏期较假手术组和抑制剂组长，差异有统计学意义（P<0.05）；空间探索实验：模型组经过目标象限的次数、距目标象限距离、目标象限时间均较假手术组和抑制剂组减少，差异有统计学意义（P<0.05）。（2）ELISA检测：与假手术组比较，模型组大鼠SOD活性降低，MDA含量及HMGB1、MMP9、TLR4表达水平均升高；与模型组比较，抑制剂组大鼠SOD活性升高，MDA含量及HMGB1、MMP9、TLR4表达水平均降低，差异均有统计学意义（P<0.05）。（3）RT-qPCR检测：模型组大鼠MMP9、HMGB1、TLR4的mRNA表达量均高于假手术组和抑制剂组，差异均有统计学意义（P<0.05）。（4）Western blot实验：模型组大鼠的HMGB1、MMP9、TLR4蛋白表达水平均高于假手术组和抑制剂组，差异均有统计学意义（P<0.05）。

HMGB1抑制剂可改善TBI大鼠的认知障碍，降低MDA、MMP9、TLR4、HMGB1的表达水平，增强SOD活性。

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.