摘要
目的:探讨虫草素对慢性阻塞性肺疾病急性加重期(AECOPD)大鼠肺损伤、炎症反应及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的影响。方法:将大鼠随机分为对照组、模型组、虫草素低剂量(80 mg/kg)组、虫草素高剂量(160 mg/kg)组和地塞米松(0.09 mg/kg)组。除对照组(14只)外,其余各组大鼠采用烟熏法联合脂多糖制备AECOPD模型,建模结束后,各组大鼠(各14只)给予对应药物干预14 d。采用全自动血气分析仪检测大鼠腹主动脉血氧分压(PaO_(2))水平;采用苏木精-伊红染色观察大鼠肺组织病理学变化并进行肺损伤评分;采用酶联免疫吸附试验检测肺组织中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;采用荧光定量聚合酶链反应和蛋白质印迹法分别检测大鼠肺组织中PI3K、Akt、mTOR信使RNA(mRNA)和蛋白水平。结果:对照组大鼠肺组织细胞排列规则,结构正常;与对照组相比,模型组大鼠肺组织肺泡破裂,有明显中性粒细胞浸润,并且可见肺泡壁增厚,且有胶原蛋白沉淀,动脉血PaO_(2)水平显著降低(P<0.05),肺损伤评分、肺组织中IL-6、TNF-α、PI3K、Akt及mTOR的mRNA和蛋白水平显著升高(P<0.05);与模型组相比,虫草素低、高剂量组大鼠肺组织肺泡壁逐渐变薄,中性粒细胞浸润程度逐渐减轻,肺泡结构逐渐趋于正常,动脉血PaO_(2)水平依次升高(P<0.05),肺损伤评分、肺组织中IL-6、TNF-α、PI3K、Akt及mTOR的mRNA和蛋白水平依次降低(P<0.05),上述差异均有统计学意义。地塞米松组与虫草素高剂量组大鼠肺组织病理学变化及各项指标水平比较,差异均无统计学意义(P>0.05)。结论:虫草素可减轻AECOPD大鼠的肺损伤,抑制炎症反应,其机制可能与抑制PI3K/Akt/mTOR信号通路的激活有关。
OBJECTIVE:To probe into the effects of cordycepin on lung injury,inflammatory reaction and phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway in rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHOD:ALL rats were randomly divided into the control group,model group,low-dose cordycepin(80 mg/kg)group,high-dose cordycepin(160 mg/kg)group and dexamethasone(0.09 mg/kg)group.Except for the control group(14 rats),the AECOPD model was prepared by fumigation method combined with lipopolysaccharide in the rest group,and each group(14 rats in each)was given corresponding drug intervention for 14 d after modeling.The partial oxygen pressure(PaO_(2))level of abdominal aorta of rats were measured by automatic blood gas analyzer;the pathologic change in lung tissue of rats were observed by hematoxylin-eosin staining and the lung injury scoring was performed;the interleukin 6(IL-6)and tumor necrosis factorα(TNF-α)in lung tissue were measured by enzyme-linked immunosorbent assay;the PI3K,Akt,mTOR messenger RNA(mRNA)and protein levels in lung tissue of rats were measured by fluorescence quantitative polymerase chain reaction and Western blotting.RESULTS:In the control group,the lung tissue cells were regularly arranged with normal structure.Compared with the control group,the alveoli of lung tissues of rats were ruptured in the model group,with obvious neutrophil infiltration and thickened alveolar walls and collagen precipitation,the arterial blood PaO_(2) level was significantly decreased(P<0.05),the lung injury score,the mRNA and protein levels of IL-6,TNF-α,PI3K,Akt and mTOR in lung tissues were significantly increased(P<0.05);compared with the model group,the alveolar walls of lung tissues were gradually thinned,the degree of neutrophil infiltration was gradually decreased,the alveolar structure was gradually normalized and the arterial blood PaO_(2) levels were increased sequentially in the low-dose and high-dose groups of cordycepi
作者
牛磊
刘建
张磊
杨静
NIU Lei;LIU Jian;ZHANG Lei;YANG Jing(Dept.of Respiratory and Critical Care Medicine,Tangshan Hongci Hospital,Hebei Tangshan 063000,China;Dept.of Critical Care Medicine,the Affiliated Hospital of North China University of Science and Technology,Hebei Tangshan 063000,China)
出处
《中国医院用药评价与分析》
2023年第7期815-819,共5页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
河北省中医药类科研指令性计划课题项目(No.2021407)。
