关键词:

脑损伤, 一氧化碳中毒, 芹菜素, 高迁移率族蛋白B1

Abstract:

Objective　To explore the effect of apigenin on regulating the miR-152/bromodomain protein 4 (BRD4) axis and inhibiting high mobility group protein B1 (HMGB1) in the treatment of carbon monoxide (CO) induced brain injury. Methods　The mouse models of CO induced brain injury were established in February 2024, and were divided into a control group, a CO treatment group, an apigenin 25 mg/kg intervention group, and an apigenin 50 mg/kg intervention group by the random number table method, with 10 in each group. The control group was intraperitoneally given air, 170 ml/kg; the CO treatment group was given intraperitoneal injection of CO, 170 ml/kg; the apigenin 25 mg/kg intervention group established the CO models 24 h, and were intraperitoneally injected apigenin, 25 mg/kg, once per day; and the 50 mg/kg apigenin intervention group established the CO models 24 h, and were intraperitoneally injected apigenin, 50 mg/kg , once per day. The mice were euthanized by 3% isoflurane anesthesia after 90 minutes, 7 days, and 14 days, respectively. The brain tissue and peripheral blood were collected. The pathological and physiological conditions of the cortical and hippocampal regions of the brain tissue were compared between the two groups, and HE staining was used for morphological observation. Immunohistochemical detection of glial fibrillary acidic protein in the brain tissue was did; the serum concentrations of HMGB1, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in the mouse serum were detected by ELISA; Western blot/real time polymerase chain reaction was used to detect the expressions of BRD4 and HMGB1/mRNA in the cells; the flow cytometry was used to detect cell apoptosis. Analysis of variance was used. Results　The expressions of GFAP protein in the control group, the CO treatment group, the apigenin 25 mg/kg intervention group, and the apigenin 50 mg/kg intervention group were (1.11±0.06), (1.93±0.18), (1.32±0.09), and (1.09±0.05), respectively, with statistical differences between the groups (all P<0.05). The concentrations of TNF-α, IL-1β, and IL-6 in the CO treatment group were higher than those in the control group and the apigenin 50 mg/kg intervention group [(1.24±0.08) pg/L vs. (0.45±0.03) pg/L vs. (0.59±0.04) pg/L, (13.56±2.30) mg/L vs. (6.30±1.23) mg/L vs. (7.69±2.10)mg/L, and (3.86±0.22) pg/L vs. (0.14±0.01) pg/L vs. (1.35±0.06) pg/L], with statistical differences (all P<0.05). The levels of HMGB1/β-actin, TNF-α/β-actin, IL-1β/β-actin, and IL-6/β-actin in the CO treatment group were higher than those in the control group and the apigenin 50 mg/kg intervention group [(1.23±0.10) vs. (0.50±0.04) vs. (0.78±0.08), (0.61±0.06) vs. (0.24±0.02) vs. (0.37±0.02), (0.85±0.14) vs. (0.42±0.05) vs. (0.52±0.02), and (1.23±0.10) vs. (0.50±0.04) vs. (0.78±0.08)], with statistical differences (all P<0.05). The apoptosis rates of hippocampal neurons in the CO treatment group, the apigenin 25 mg/kg intervention group, and the apigenin 50 mg/kg intervention group were higher than that in the control group [(19.92±3.25)%, (15.63±2.25)%, and (11.23±3.55)% vs. (4.98±1.26)%], with statistical differences (all P<0.05). Conclusion　Apigenin inhibits the expression of HMGB1 by regulating the miR-152/BRD4 axis, and alleviates brain damage caused by carbon monoxide poisoning.

Key words:

Brain injury, Carbon monoxide poisoning, Apigenin, High mobility group protein B1