氨茶碱对慢性阻塞性肺疾病大鼠肺功能的改善作用  

Role of aminophylline in improving lung function in rats with chronic obstructive pulmonary disease

作　　者：张欣[1] 杜文秀[1] 刘芳[1] 杜俊凤[1] 张颖 迟玉敏[1] ZHANG Xin;DU Wen-xiu;LIU Fang;DU Jun-feng;ZHANG Ying;CHI Yu-min(Department of Respiration,Cangzhou Central Hospital,Cangzhou,Hebei 061000,China)

机构地区：[1]沧州市中心医院呼吸科,河北沧州061000

出　　处：《中华实用诊断与治疗杂志》2021年第9期906-911,共6页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河北省2020年度医学科学研究课题计划(20200338)。

摘　　要：目的观察慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)大鼠应用氨茶碱处理后肺功能及支气管肺泡灌洗液白细胞介素(interleukin, IL)-6、IL-1β、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)水平变化,探讨氨茶碱经PI3K/Akt/mTOR通路对COPD大鼠肺损伤的改善作用及对炎症的抑制作用。方法 SPF级SD大鼠55只,其中8只为对照组,余47只采用烟熏+气道注入脂多糖法制备COPD模型,将40只造模成功大鼠随机分为模型组、激动剂组、氨茶碱组、激动剂+氨茶碱组各10只。造模成功次日,激动剂组给予PI3K激动剂740 Y-P溶液灌胃,氨茶碱组给予氨茶碱溶液灌胃,激动剂+氨茶碱组给予740 Y-P+氨茶碱混合溶液灌胃,均1 mL/(100 g·次),1次/d,连续30 d;对照组和模型组灌注等量生理盐水。干预结束,测定各组大鼠用力肺活量(forced vital capacity, FVC)、第0.1秒用力呼气容积(forced expiratory volume in the first 0.1 second, FEV_(0.1));然后取支气管肺泡灌洗液,采用ELISA法检测IL-6、IL-1β、TNF-α水平;取右肺组织行HE染色观察病理变化,采用TUNEL法检测肺泡上皮细胞凋亡率;取左肺组织,采用Western blot法检测PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR、LC3-Ⅱ蛋白表达。结果激动剂组、模型组、激动剂+氨茶碱组、氨茶碱组大鼠FVC[(2.11±0.10)、(2.98±0.12)、(4.75±0.13)、(6.05±0.17) mL]、FEV_(0.1)[(0.52±0.11)、(0.96±0.12)、(2.46±0.14)、(3.77±0.16) mL]均低于对照组[(7.64±0.31)、(4.52±0.16) mL](P<0.05),支气管肺泡灌洗液IL-6[(5.88±0.27)、(4.91±0.23)、(3.45±0.14)、(2.81±0.11) ng/L]、IL-1β[(7.95±0.22)、(7.04±0.16)、(6.36±0.19)、(3.95±0.11) ng/L]、TNF-α[(9.22±0.35)、(8.49±0.14)、(6.44±0.20)、(4.71±0.23 ng/L)]水平均高于对照组[(2.37±0.19)、(2.02±0.10)、(1.65±0.18)ng/L](P<0.05),肺泡上皮细胞凋亡率[(80.42±3.24)%、(65.34±4.48)%、(34.98±3.16)%、(16.36±2.14)%]均高于对照组[(1.98±0.12)%](P<0.05);激动剂组、Objective To observe the changes of lung function and levels of interleukin(IL)-6, IL-1β and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid(BALF) of rats with chronic obstructive pulmonary disease(COPD) after treatment with aminophylline,and to investigate the role of aminophylline in alleviating lung injury and inhibiting inflammation via PI3 K/Akt/mTOR pathway.Methods In 55 SPF SD rats,47 rats were prepared COPD models by smoking and intratracheal injecting lipopolysaccharide,in which 40 were successfully prepared COPD rat models and were randomly divided into model group,agonist group,aminophylline group and agonist+aminophylline group,with 10 rats in each group.Another 8 SD rats were as controls(control group).On the second day of modeling,agonist group,aminophylline group and agonist+aminophylline group received lavage with PI3 K agonist,aminophylline and PI3 K agonist+aminophylline solution respectively,1 mL/100 g each time,once a day,totally for 30 d.Control group and model group received lavage with equivalent volume of normal saline.After intervention,the forced vital capacity(FVC)and forced expiratory volume in the first 0.1 second(FEV_(0.1))were detected in each group.The levels of IL-6,IL-1βand TNF-αin BALF were detected by ELISA.HE staining was used to observe the right lung histopathological changes.TUNEL method was used to detect the apoptosis rate of the lung tissue.Western blot was used to detect the expressions of PI3 K,p-PI3 K,Akt,p-Akt,mTOR,p-mTOR and LC3-Ⅱ proteins of the left lung.Results The values of FVC((2.11±0.10),(2.98±0.12),(4.75±0.13),(6.05±0.17)mL)and FEV_(0.1)((0.52±0.11),(0.96±0.12),(2.46±0.14),(3.77±0.16)mL)in agonist group,model group,agonist+aminophylline group and aminophylline group were lower than those in control group((7.64±0.31),(4.52±0.16)mL)(P<0.05),the levels of IL-6((5.88±0.27),(4.91±0.23),(3.45±0.14),(2.81±0.11)ng/L),IL-1β((7.95±0.22),(7.04±0.16),(6.36±0.19),(3.95±0.11)ng/L)and TNF-α((9.22±0.35),(8.49±0.14),(6.44±0.20),(4.

关 键 词：慢性阻塞性肺疾病 氨茶碱 PI3K/Akt/mTOR通路 炎症 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统]