白花败酱草总黄酮对实验性急性肺损伤模型大鼠的肺保护作用及其机制  

Lung protection and mechanism of total flavonoids from Patrina villosa Juss in an experimental model of acute lung injury in rats

作　　者：李建波[1] 冯海英[2] 张洁[1] 刘明[3] 贾海波[4] 赵伟鹏 LI Jianbo;FENG Haiying;ZHANG Jie;LIU Ming;JIA Haibo;ZHAO Weipeng(Department of Traditional Chinese Medicine,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050000,China;Department of Hematology and Oncology,Huanghua People's Hospital of Hebei Province,Huanghua 061113,China;Department of Radiation Oncology,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050000,Chi-na;Department of Traditional Chinese Medicine,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学第四医院中医科,河北石家庄050000 [2]河北省黄骅市人民医院血液肿瘤科,河北黄骅061113 [3]河北医科大学第四医院放疗科,河北石家庄050000 [4]河北省人民医院中医科,河北石家庄050051

出　　处：《中国病理生理杂志》2024年第7期1230-1236,共7页Chinese Journal of Pathophysiology

基　　金：河北省中医药管理局科研计划项目(No.2022395);国家中医药管理局第七批全国老中医药专家学术经验继承工作项目(国中医药办人教函[2022]76号)。

摘　　要：目的:探讨白花败酱草总黄酮(total flavoniods from Patrina villosa Juss,PJF)对实验性急性肺损伤(acute lung injury,ALI)模型大鼠的肺保护作用及其潜在机制。方法:用气管内滴注5 mg/kg脂多糖(lipopolysaccharide,LPS)构建ALI大鼠模型。将60只雄性SD大鼠随机分为对照组、LPS组、LPS+低剂量(100 mg/kg)PJF组和LPS+高剂量(300 mg/kg)PJF组(后2组在ALI造模前1 h给予PJF灌胃),每组15只。造模后24 h,收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织。HE染色显示肺组织形态;干湿称重法测量肺组织的湿/干重比;伊文思蓝染色评估肺组织中上皮屏障的通透性;ELISA检测BALF中炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)和IL-6含量,以及肺组织中氧化应激指标超氧化物歧化酶(superoxide dismutase,SOD)、髓过氧化物酶(myeloperoxidase,MPO)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性及丙二醛(malondialdehyde,MDA)含量;免疫印迹法检测肺组织中C/EBP同源蛋白(C/EBP homologous protein,CHOP)、葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)和X框结合蛋白1(X-box binding protein 1,XBP1)蛋白表达。结果:与对照组比较,LPS组大鼠肺组织呈现肺泡结构不清和大量炎症细胞浸润,ALI评分和肺组织的湿/干重比显著升高(P<0.05),BALF中IL-6、IL-1β和TNF-α水平,以及肺组织中MDA含量、MPO活性及CHOP、GRP78和XBP1蛋白表达水平显著升高(P<0.05),肺组织中SOD和GSH-Px活性显著降低(P<0.05)。与LPS组比较,PJF干预组肺组织形态改善,ALI评分和肺组织的湿/干重比显著下降(P<0.05),BALF中IL-6、IL-1β和TNF-α水平,以及肺组织中MDA含量、MPO活性及CHOP、GRP78和XBP1蛋白表达水平显著降低(P<0.05),肺组织中SOD和GSH-Px活性显著升高(P<0.05);且高剂量组的效果明显优于低剂量组。结论:PJF对ALI大鼠具有肺保护作用,其机制可能与抑制炎症反应、氧化应AIM:To investigate the protective effect of total flavonoids from Patrina villosa Juss(PJF)on the lung in an experimental rat model of acute lung injury(ALI),and to elucidate the potential mechanism.METHODS:The ALI rat model was established by instilling 5 mg/kg of lipopolysaccharide(LPS)into the airway.Sixty male SD rats were randomly divided into 4 groups:control,LPS,LPS+low-dose PJF(receiving 100 mg/kg PJF one hour before ALI modeling)and LPS+high-dose PJF(receiving 300 mg/kg PJF one hour before ALI modeling).Each group consisted of 15 animals.Lung tissues and bronchoalveolar lavage fluid(BALF)were collected from all groups 24 h after modeling.For assessment of lung tissue morphology,HE staining was performed.The wet/dry weight ratio of the lung tissue was determined using the wet/dry weighing method.Evans blue staining was conducted to assess epithelial barrier permeability in lung tissues.ELISA was used to detect the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in the BALF,as well as oxidative stress markers including superoxide dismutase(SOD),myeloperoxidase(MPO)and glutathione peroxidase(GSH-Px)activity,and malondialdehyde(MDA)content in the lung tissue.The expression levels of C/EBP homologous protein(CHOP),glucose-regulated protein 78(GRP78)and X-box binding protein 1(XBP1)in the lung tissue were analyzed by Western blotting.RESULTS:Compared with control group,the rats in LPS group exhibited a blurred alveolar structure with a significant infiltration of inflammatory cells.The ALI score and the wet/dry weight ratio of the lung tissue were increased(P<0.05).Concurrently,the levels of IL-6,IL-1βand TNF-αin the BALF,along with MDA content and MPO activity in the lung tissue,were elevated(P<0.05).Additionally,the protein levels of CHOP,GRP78 and XBP1 were up-regulated in the lung tissue(P<0.05),while the SOD and GSH-Px activity was significantly decreased(P<0.05).Compared with LPS group,PJF intervention exerted beneficial effects on the lung tissue morphol

关 键 词：白花败酱草总黄酮 急性肺损伤 炎症 氧化应激 内质网应激 

分 类 号：R563[医药卫生—呼吸系统] R285.5[医药卫生—内科学] R363.2[医药卫生—临床医学]