关键词:

哮喘, 蛋白激酶B/叉头框蛋白O3/核转录因子-κB信号轴, CD147, 气道重塑, 动物实验

Abstract:

Objective　To investigate the mechanism of CD147 in regulating airway remodeling in asthma rats based on the protein kinase B/forkhead box protein O3/nuclear factor-κB (Akt-FoxO3-NF-κB) signaling axis. Methods　Seventy SPF-grade SD rats were selected, aged 7-8 weeks, weight (200±20) g. Control group, model group, IgG group, anti-CD147 group and anti-CD147+SC-79 group, 12 rats in each group. In the anti-CD147+SC-79 group, 7 mg/kg of CD147 antibody was intraperitoneally injected and 0.04 μg/kg of SC-79 was injected through the tail vein. In the anti-CD147 group, 7 mg/kg of CD147 antibody was intraperitoneally injected and the same amount of normal saline was injected through the tail vein. In the IgG group, 7 mg/kg of IgG was intraperitoneally injected and the same amount of normal saline was injected through the tail vein. Both the control group and the model group were intraperitoneally injected and tail vein injected with the same amount of normal saline. Once a day, with continuous intervention for 4 weeks. The airway resistance (nebulized inhalation of different concentrations of acetylcholine), the number of inflammatory cells, the levels of inflammatory factors, the pathological changes of lung tissue, the expressions of transforming growth factor -β1 (TGF-β1) and α -smooth muscle actin (α-SMA), and the expressions of Akt-FoxO3-NF-κB signal axis-related proteins were compared 24 hours after the last administration in each group. One-way analysis of variance and SNK-q test were used for statistical analysis. Results　After aerosol inhalation of different concentrations of acetylcholine, the airway resistance of the model group was higher than that of the control group (P<0.05). The airway resistance of anti-CD147 group was lower than that of IgG group (P<0.05). The airway resistance of anti-CD147+SC-79 group was higher than that of anti-CD147 group (P<0.05). The numbers of macrophages, lymphocytes, neutrophils and eosinophils in the model group were higher than those in the control group (all P<0.05). The numbers of macrophages, lymphocytes, neutrophils and eosinophils in anti-CD147 group were lower than those in IgG group (all P<0.05). The numbers of macrophages, lymphocytes, neutrophils and eosinophils in anti-CD147+SC-79 group were higher than those in anti-CD147 group (all P<0.05). The levels of IL-4, IL-5 and IL-13 in the model group were higher than those in the control group (all P<0.05). The levels of IL-4, IL-5 and IL-13 in anti-CD147 group were lower than those in IgG group (all P<0.05). The levels of IL-4, IL-5 and IL-13 in anti-CD147+SC-79 group were higher than those in anti-CD147 group (all P<0.05). The expressions of TGF-β1 and α-SMA in the model group were higher than those in the control group (0.89±0.09 vs. 0.36±0.04, 0.80±0.09 vs. 0.27±0.03) (both P<0.05). The expressions of TGF-β1 and α-SMA in anti-CD147 group were lower than those in IgG group (0.47±0.05 vs. 0.85±0.09, 0.34±0.04 vs. 0.77±0.08) (both P<0.05). The expressions of TGF-β1 and α-SMA in anti-CD147+SC-79 group were higher than those in anti-CD147 group (0.80±0.09 vs. 0.47±0.05, 0.72±0.08 vs. 0.34±0.04) (both P<0.05). The expression of p-Akt/Akt, p-FoxO3a/FoxO3a, p-NF-κB p65/NF-κB p65 in model group were higher than those in the control group (0.93±0.10 vs. 0.44±0.05, 0.86±0.09 vs. 0.37±0.04, 0.76±0.08 vs. 0.33±0.04) (all P<0.05). The expression of p-Akt/Akt, p-FoxO3a/FoxO3a, p-NF-κB p65/NF-κB p65 in anti-CD147 group were lower than those in the IgG group (0.48±0.05 vs. 0.90±0.10, 0.41±0.05 vs. 0.82±0.09, 0.38±0.04 vs. 0.74±0.08) (all P<0.05). The expression of p-Akt/Akt, p-FoxO3a/FoxO3a, p-NF-κB p65/NF-κB p65 in anti-CD147+SC-79 group were higher than those in the anti-CD147 group (0.87±0.09 vs. 0.48±0.05, 0.79±0.08 vs. 0.41±0.05, 0.70±0.08 vs. 0.38±0.04) (all P<0.05). Conclusion　CD147 antibody can alleviate airway remodeling in asthma rats and is associated with inhibition of the Akt-FoxO3-NF-κB signaling axis.

Key words:

Asthma,  , Protein kinase B/forkhead box protein O3/nuclear factor-κB signaling axis,  , CD147,  , Airway remodeling, 　Animal experiment