五味子哮喘汤对哮喘小鼠SIRT1/Akt信号通路及肺功能的影响  

Effects of Schisandrae-asthma decoction on SIRT1/Akt signaling path⁃way and lung function in asthmatic mice

作　　者：孙毅[1] 任亚平 孔乔 陈辉[1] SUN Yi;REN Ya-ping;KONG Qiao;CHEN Hui(Department of Pharmacy,Tengzhou Central People's Hospital,Tengzhou 277599,China;Department of Traditional Chinese Medicine,Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100029,China)

机构地区：[1]滕州市中心人民医院药剂科,山东滕州277599 [2]北京中医药大学东直门医院中医科,北京100029

出　　处：《中国病理生理杂志》2021年第3期481-486,共6页Chinese Journal of Pathophysiology

基　　金：山东省2019-2020年度中医药科技发展计划项目(No.2019-0661)。

摘　　要：目的:探究五味子哮喘汤(Schisandrae-asthma decoction)对哮喘小鼠沉默信息调节因子1(silent information regulator 1,SIRT1)/蛋白激酶B(protein kinase B,PKB/Akt)信号通路及肺功能的影响。方法:BALB/c小鼠随机分为对照组、模型组、阳性对照地塞米松(10 mg/kg)组及低剂量(8.5 g/kg)、中剂量(17 g/kg)和高剂量(34 g/kg)五味子哮喘汤组,每组20只。除对照组外其余5组采用卵清蛋白+氢氧化铝刺激制备哮喘模型,对照组予以等量生理盐水注射及雾化吸入,于第16天进行药物干预,每天1次,连续灌胃7 d。末次给药后24 h,肺功能仪检测各组小鼠肺功能指标0.1 s用力呼气容积(forced expiratory volume in 0.1 s,FEV0.1)及最高呼气流速(peak expiratory flow rate,PEFR),HE染色检测小鼠肺组织病理学变化,RT-qPCR和Western blot检测肺组织SIRT1、磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)及Akt的mRNA和蛋白表达。结果:与对照组比较,模型组小鼠FEV0.1和PEFR水平及肺组织SIRT1 mRNA和蛋白表达均显著降低,PI3K和Akt mRNA及p-PI3K/PI3K和p-Akt/Akt蛋白水平均显著升高(P<0.05),肺组织周围可见大量炎症细胞浸润;与模型组比较,地塞米松组和各剂量五味子哮喘汤组小鼠FEV0.1和PEFR水平及肺组织SIRT1 mRNA和蛋白表达均显著增加,PI3K和Akt mRNA及p-PI3K/PI3K和p-Akt/Akt蛋白水平均显著降低(P<0.05),肺组织病变呈不同程度减轻。结论:五味子哮喘汤可改善哮喘小鼠肺功能,减轻哮喘症状,可能与调控SIRT1/Akt信号通路有关。AIM:To explore the effects of Schisandrae-asthma decoction(SAD)on silent information regulator 1(SIRT1)/protein kinase B(PKB/Akt)signaling pathway and lung function in asthmatic mice.METHODS:BALB/c mice were randomly divided into control group,model group,positive control dexamethasone(Dex;10 mg/kg)group,low-dose(8.5 g/kg)SAD group,middle-dose(17 g/kg)SAD group and high-dose(34 g/kg)SAD group,with 20 mice in each group.Except control group,the animals in other 5 groups were stimulated with ovalbumin(OVA)and aluminum hydroxide[Al(OH)3],while the animals in control group was given equal amount of normal saline injection and aerosol inhalation.The drug intervention was carried out on the 16th day,once a day for 7 consecutive days.At 24 h after the last administration,the lung function indexes,including forced expiratory volume in 0.1 s(FEV0.1)and peak expiratory flow rate(PEFR),of the mice in each group were detected by pulmonary function instrument,HE staining was used to detect the pathological changes of lung tissue,and the mRNA and protein levels of SIRT1,phosphatidylinositol 3-kinase(PI3K)and Akt were determined by RT-qPCR and Western blot.RESULTS:Compared with control group,FEV0.1 and PEFR level,and SIRT1 expression at mRNA and protein levels in the lung tissues of model group were significantly decreased,the mRNA levels of PI3K and Akt and the protein levels of p-PI3K/PI3K and p-Akt/Akt were significantly increased(P<0.05),and a large number of inflammatory cells were seen around the lung tissue.Compared with model group,the levels of FEV0.1 and PEFR,and the expression of SIRT1 at mRNA and protein levels in the lung tissues of Dex group,low-dose SAD group,middle-dose SAD group and high-dose SAD group were significantly increased,the mRNA levels of PI3K and Akt and the protein levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased(P<0.05),and the pathological changes of the lung tissues were alleviated in different degrees.CONCLUSION:Schisandrae-asthma decoction improves lung function and alleviates

关 键 词：哮喘 五味子哮喘汤 SIRT/Akt信号通路 肺功能 

分 类 号：R285.5[医药卫生—中药学] R562.25[医药卫生—中医学]