摘要
目的:研究泽漆汤通过磷脂酰肌醇3-激酶(PI3K)/丝苏氨酸激酶(AKT)通路对慢性阻塞性肺疾病(COPD)小鼠肺功能及中性粒细胞胞外诱捕网(NETs)的调控作用。方法:将32只BALB/c雄性小鼠随机分为对照组、模型组、泽漆汤组和地塞米松组,各8只。除对照组外,其余3组均采用香烟烟雾吸入法建立COPD模型,连续12周;第9~12周,对照组和模型组给予0.9%氯化钠溶液0.2 mL/(kg·d)灌胃,泽漆汤组给予0.171 g/mL泽漆汤0.2 mL/(kg·d)灌胃、地塞米松组给予地塞米松2 mg/(kg·d)灌胃。检测各组小鼠0.3 s内用力呼气容积(FEV0.3)/用力肺活量(FVC)、每分钟通气量(MV)、气道狭窄指数(Penh),肺泡平均截距(MLI)、支气管壁厚度(BWT),血清及肺组织中白细胞介素(IL)-2、IL-6、IL-17A、IL-18水平,肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平、中性粒细胞弹性蛋白酶(NE)、瓜氨酸化组蛋白H3(Cit H3)、磷酸化PI3K(p-PI3K)、磷酸化AKT(p-AKT)表达水平及髓过氧化物酶(MPO)-DNA复合物的含量。结果:干预4周后,模型组小鼠FEV0.3/FVC、MV、SOD、GSH-PX均低于对照组(P<0.05),Penh、MLI、BWT、IL-2、IL-6、IL-17A、IL-18、MDA、NE、Cit H3、MPO-DNA、p-PI3K、p-AKT均高于对照组(P<0.05);泽漆汤组和地塞米松组小鼠FEV0.3/FVC、MV、SOD、GSH-PX均高于模型组(P<0.05),Penh、MLI、BWT、IL-2、IL-6、IL-17A、IL-18、MDA、NE、Cit H3、MPO-DNA、p-PI3K、p-AKT均低于模型组(P<0.05);泽漆汤组小鼠NE、Cit H3、MPO-DNA、p-PI3K、p-AKT均低于地塞米松组(P<0.05),其余指标与地塞米松组比较,差异无统计学意义(P>0.05)。结论:泽漆汤可改善COPD小鼠的肺功能及肺组织病理改变、减轻炎症反应和氧化应激反应,抑制PI3K/AKT通路介导的NETs形成可能是相关的分子机制。
Objective:To study the regulation effect of Zeqi Decoction on the lung function and neutrophil extracellular traps(NETs)in mice with chronic obstructive pulmonary disease(COPD)through phosphatidylinositol 3-kinase(PI3K)/serine threonine kinase(AKT)signaling pathway.Methods:A total of 32 BALB/c male mice were randomly divided into the control group,the model group,Zeqi Decoction group and Dexamethasone group,with eight mice in each group.Except for the control group,the COPD model was established by cigarette smoke inhalation for 12 weeks in the other three groups;from the 9th to 12th week,the control group and the model group were given 0.9%sodium chloride solution at a dosage of 0.2 mL/(kg·d)by gastric gavage,Zeqi decoction group was given 0.171 g/mL Zeqi Decoction at a dosage of 0.2 mL/(kg·d)by gastric gavage,and Dexamethasone group was given Dexamethasone at a dosage of 2 mg/(kg·d)by gastric gavage.The forced expiratory volume in 0.3 s(FEV0.3)/forced vital capacity(FVC),minute ventilation volume(MV),enhanced pause(Penh),mean linear intercept(MLI)in lung tissue,bronchial wall thickness(BWT),the levels of interleukin(IL)-2,IL-6,IL-17 A and IL-18 in serum and lung tissue,the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),the expression levels of neutrophil elastase(NE),citrullinated histone H3(Cit H3),phosphorylated PI3K(p-PI3K),phosphorylated AKT(p-AKT)and the content of myeloperoxidase(MPO)-DNA complex in lung tissue were detected.Results:After four weeks of intervention,the FEV0.3/FVC,MV,SOD and GSH-PX of the mice in the model group were lower than those of the mice in the control group(P<0.05),and the Penh,MLI,BWT,IL-2,IL-6,IL-17 A,IL-18,MDA,NE,Cit H3,MPO-DNA,p-PI3K and p-AKT were higher than those of the mice in the control group(P<0.05);the FEV0.3/FVC,MV,SOD and GSH-PX of the mice in Zeqi Decoction group and Dexamethasone group were higher than those of the mice in the model group(P<0.05),and the Penh,MLI,BWT,IL-2,IL-6,IL-17 A,IL-18,MDA,NE,Cit H3,MPO-DNA,p-PI3K and p-AKT were lower than those of the mice in the model group(P<0.05);the levels of NE,Cit H3,MPO-DNA,p-PI3K and p-AKT in Zeqi Decoction group were lower than those of the mice in Dexamethasone group(P<0.05),and there was no statistically significant difference being found in the comparisons of remaining indexes between Zeqi Decoction group and Dexamethasone group(P>0.05).Conclusion:Zeqi Decoction can improve the lung function and pathological changes of lung tissue in COPD mice,and reduce the inflammatory responses and oxidative stress.Its inhibition of the NETs formation mediated by PI3K/AKT signaling pathway may be the related molecular mechanism.
作者
张宇静
陆元勋
冯慧
ZHANG Yujing;LU Yuanxun;FENG Hui(Department of Geriactrics,Ningbo Beilun District Hospital of Chinese Medicine,Ningbo Zhejiang 315800,China;Department of Research,Ningbo Mingbei Chinese Medicine Co.,Ltd.,Ningbo Zhejiang 315010,China;Department of Chinese Medicine,The Affiliated People's Hospital of Ningbo University,Ningbo Zhejiang 315040,China)
出处
《新中医》
2025年第13期228-234,共7页
New Chinese Medicine
基金
浙江省中医药科技计划项目(2025ZX180)。
