目的 探讨和厚朴酚通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路对哮喘小鼠的作用及其对Toll样受体2（TLR2）、TLR4表达的影响。方法 50只ICR小鼠随机分为对照组、哮喘模型组、阳性对照组（地塞米松10 mg/kg）及和厚朴酚高、低剂量（50、10 μg/kg）组。采用卵清蛋白（OVA）+氢氧化铝致敏法诱导哮喘模型，随后ip相应的药物进行干预，连续给药7 d，于末次给药后24 h取肺泡灌洗液进行白细胞分类并计数；取左侧肺组织进行HE、PAS、Masson染色常规病理组织学检查；采用Western blotting法检测小鼠肺组织PI3K、Akt、磷酸化蛋白激酶B（p-Akt）、TLR2、TLR4蛋白的表达水平；采用RT-PCR法检测小鼠肺组织中TLR2、TLR4 mRNA的表达水平。结果 与模型组比较，和厚朴酚50 μg/kg组小鼠肺泡灌洗液中性粒细胞、淋巴细胞、嗜酸性粒细胞计数均减少（P<0.01）；肺组织病理明显改善，炎症细胞浸润减少，气管壁及肺泡损伤明显缓解；肺组织PI3K、Akt、p-Akt、TLR2、TLR4蛋白及TLR2、TLR4 mRNA表达水平下调（P<0.05）。结论 和厚朴酚对OVA致哮喘小鼠的炎症反应具有较好的抑制作用，其机制可能与作用于TLR2、TLR4受体进而抑制PI3K/Akt信号通路有关。

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.

R285.5

国家自然科学基金面上项目（31570357）；河南省高等学校重点科研项目计划（17A310011）