Effects of Honokiol on airway inflammation in asthmatic mice exposed to PM2.5 and its mechanism / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the protective effect of Honokiol on the airway inflammation induced by particulate matter 2.5(PM2.5)in the asthmatic mice and its mechanism.Methods Fifty male specific pathogen free (SPF)Balb/c mice were randomly divided into 5 groups.Group Anormal control group;group Basthmatic model group;group CPM2.5 exposure asthmatic group;group DTAK -242 group;group EHonokiol group. Asthmatic mouse models were established by ovalbumin(OVA)sensitization and challenge.On days 0 and 7,the mice in B-E groups were injected intraperitoneally with injection 100 mg/L OVA and aluminum hydroxide for sensitization;on days 14 to 21,10 g/L OVA solution was given 30 min per day to challenge.During challenge phrase,the mice in C -E groups received intratracheal injection of PM2.5,every other day,4 times totally.On this basis,the mice in group D re-ceived TAK-242 intraperitoneal injection,and the mice in group E received honokiol intragastric administration.Group A was given saline instead of OVA.Animals were sacrificed 24 h after the final inhalation challenge,and the bronchoal-veolar lavage fluid(BALF)of the left lung was used for differential inflammatory cell counts.The expressions of Toll-like receptors 4(TLR4)and nuclear factor(NF)-κB at mRNA level were detected by real-time quantitative PCR. Flow cytometry analysis was performed to measure the levels of Th17 and Treg cells.Results Compared with group A,mice in group B and group C expressed more serious disorders of bronchial epithelial cells,alveolar wall congestion and edema,increased mucus secretion in the airway and infiltration of inflammatory cells in the lung,and those in group C were more obvious than those of group B and group E significantly reduced respiratory inflammation;compared with group A[(4.15 ± 1.35)×108/L,0.012 0 ± 0.002 3],the total number of inflammatory cell counts[(16.79 ± 5.62)×108/L and(24.58 ± 13.46)×108/L],eosinophils proportions(0.113 8 ± 0.022 3 and 0.197 8 ± 0.084 9)in group B and group C,were significantly higher,and the differences were statistically significant(all P<0.05);The total number of inflammatory cell counts and eosinophils proportion in group E(8.56 ± 3.28)×108/L and 0.041 5 ± 0.013 5)were significantly lower than those in group C,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group B and C(1.85 ± 0.56,1.82 ± 0.28 and 2.97 ± 0.41,2.83 ± 0.32)were significantly higher,and the differences were statistically significant(all P <0.05);The expressions of TLR4 mRNA and NF-κB mRNA in group E(1.60 ± 0.28,1.54 ± 0.25)was significantly lower than those in group C,and the differences were statistically significant(all P<0.05);the expressions of Th17 in group B and C[(2.89 ± 0.61)% and(4.96 ± 0.27)%]were significantly higher than those of group A[(1.03 ± 0.35)%] (all P<0.05);The expression of Th17 in group E[(1.83 ± 0.23)%]was significantly lower than that of group C,and the differences were statistically significant(P<0.05);the expressions of Treg in group B and C[(4.96 ± 0.35)%and(2.27 ± 0.41)%]were significantly lower than those of group A[(7.37 ± 0.56)%],and the differences were sta-tistically significant(all P<0.05);The expression of Treg in group E was significantly increased[(6.45 ± 0.38)%] compared with that in group C,and the difference were statistically significant(P<0.05);and those of group D and E were improved remarkably.Conclusions Honokiol can relieve PM2.5 exposure of asthmatic airway inflammation through down-regulating the expression of TLR4 and NF-κB and Th17 and regulating the balance of Th17 and Treg cells.