ABSTRACT
Objective: To investigate the effect of honokiol on PI3K/Akt signaling pathway in asthmatic mice and its effect on TLR2 and TLR4 expression. Methods Fifty ICR mice were randomly divided into normal control group, asthma model group, positive control group (dexamethasone 10 mg/kg, ip), and honokiol high and low dose (50 μg/kg and 10 μg/kg, ip) groups. The asthma model was induced by ovalbumin plus aluminum hydroxide sensitization method, and then the corresponding drugs were administered for 7 d. The alveolar lavage fluid was collected and white blood cells were counted at 24 h after the last administration; The histopathological examinations of HE, PAS and Masson staining were performed. The expression of PI3K, Akt, p-Akt, TLR2, and TLR4 protein in lung tissue was detected by Western blotting. The mRNA expression of TLR2 and TLR4 in lung tissue of mice was detected by RT-PCR. Results Compared with the asthma model group, the numbers of neutrophil, lymphocyte and eosinophil in the alveolar lavage fluid of mice treated with honokiol 50 μg/kg group were significantly reduced (P < 0.01); Lung pathology was significantly improved, and inflammatory cell infiltration was significantly reduced (P < 0.05). The tracheal wall and alveolar damage were significantly relieved; The expression levels of PI3K, Akt, p-Akt, TLR2, TLR4 protein and TLR2, TLR4 mRNA were significantly down-regulated in lung tissue (P < 0.05). Conclusion Honokiol has a good inhibitory effect on OVA-induced inflammatory response in asthmatic mice. The mechanism may be related to the inhibition of PI3K/Akt signaling pathway by TLR2 and TLR4 receptors.
ABSTRACT
Objective To evaluate the effects of PM2.5 on the differentiation of splenic CD4 + T lymphocytes in acute asthma mice.Methods (1) Mouse models of acute asthma were established by ovalbumin (OVA) sensitization and challenge.(2) PM2.5 was collected in the urban area of Zhanjiang city under heavy traffic and serious air pollution from total suspended particulate(TSP) mid-flow sampler and multistage particles cutters and the dry powder of PM2.5 was prepared.(3) Specific-pathogen free Balb/c mice,female,at 6 to 8 weeks of age were randomly divided into 8 groups (8 mice each group):a negative control group (NC group),asthma control group (AC group),sensitized mice treated with different doses of PM2.5 groups (SP groups) and asthmatic mice treated with different doses of PM2.5 groups (AP groups).SP groups and AP groups were respectively divided into 3 subgroups according to the dose of PM2.5.The AC group,SP groups and AP groups were sensitized on D0,D7 and D14,and the NC group was treated with NS as controls.The SP1/AP1 group,SP2/AP2 group and SP3/AP3 group were respectively given 50 μL PM2.5 suspension.NC group and AC group were instilled with NS as controls.AC group and AP groups were challenged by aerosol of OVA,and NC group and SP group were treated with NS as controls.Twenty-four hours after last challenge,all the mice were sacrificed,and the percentage of regulatory T cells (Treg),T helper cell type 1 (Th1),Th2 and Th17 of splenic CD4 + T lymphocytes was detected by flow cytometry (FCM).Results (1) An OVA-induced mouse models with acute asthma were successfully established.(2) Comparison of the percentage of Treg of splenic CD4 + T lymphocytes:SP group [(12.28 ± 0.73) ％,(11.93 ± 0.81) ％ and (11.70-± 1.14) ％] and AC group [(12.18 ± 1.00) ％] were lower than that in the NC group[(13.50 ± 0.39) ％] (P ＜ 0.05),AP3 group [(10.58 ± 0.65) ％] was lower than that in the AC group and AP1 group [(11.91 ± 0.79) ％] (P ＜ 0.05).(3) Comparison of the ratio of Th1/Th2 of splenic CD4+ T lymphocyte:SP1 group [(7.74 ± 1.21)％] was higher than that in the NC group [(5.52 ± 1.06) ％] (P ＜0.05),SP2 group[(6.30 ±0.58) ％] was lower than that in the SP1 group(P ＜0.05),SP3 group [(4.87 ± 0.82) ％] was lower than that in the SP2 group (P ＜ 0.05);AC group [(3.69-± 0.47) ％] was lower than that in the NC group and SP3 group (P ＜ 0.05);AP3 group [(2.92 ± 0.57) ％] was lower than that in the AC group(P ＜ 0.05).(4) Comparison of the percentage of Th17 of splenic CD4+ T lymphocyte:AP3 group [(1.46 ± 0.39) ％] was higher than that in the NC group [(0.89 ± 0.24) ％] and the AP2 group [(0.83 ± 0.15) ％] (P ＜ 0.001).Conclusions PM2.5 can inhibit splenic CD4 + T lymphocyte of acute asthma mice differentiation into Treg and Th1,and promote their differentiation into Th2 and Th17,through which aggravates inflammation reactions in the airway.