实用医学杂志 ›› 2023, Vol. 39 ›› Issue (10): 1218-1223.doi: 10.3969/j.issn.1006⁃5725.2023.10.005

• 基础研究 • 上一篇    下一篇

姜辣素对脂多糖诱导的大鼠急性呼吸窘迫综合征肺泡过度促凝及纤溶抑制的防治作用 

李清1 古家润2 肖川1 沈锋1 刘颖1 李璐1 何娟1 李伟1 李书文1 刘博1 陈先俊1    

  1. 贵州医科大学附属医院1 重症医学科,2 急诊医学科(贵阳 550004) 
  • 出版日期:2023-05-25 发布日期:2023-05-25
  • 通讯作者: 沈锋 E⁃mail:doctorshenfeng@163.com
  • 基金资助:
    国家自然科学基金项目(编号:82160365);贵州省卫生健康委科学技术项目(编号:gzwkj2021⁃034)

Effects of gingerol on alveolar hypercoagulation and fibrinolytic inhibition in rats with LPS⁃induced acute respiratory distress syndrome 

LI Qing*,GU Jiarun,XIAO Chuan,SHEN Feng,LIU Ying,LI Lu,HE Juan, LI Wei,LI Shuwen,LIU Bo,CHEN Xianjun.   

  1. Department of Critical Care Medicine,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China 
  • Online:2023-05-25 Published:2023-05-25
  • Contact: SHEN Feng E⁃mail:doctorshenfeng@163.com

摘要:

目的 探索姜辣素对脂多糖(LPS)诱导的急性呼吸窘迫综合征(ARDS)大鼠肺泡过度促凝 和纤溶抑制的防治效果及可能机制。方法 雄性 SD 大鼠按随机数字表法分为对照组、LPS 组、不同剂量 姜辣素组(10、20、30 m/kg),共 5 组。采用 LPS 气管内雾化吸入复制大鼠 ARDS 模型,腹腔内注射不同剂量姜辣素处理。通过 HE 染色观察大鼠肺组织病理学变化;评价肺组织损伤程度;计算肺组织湿/干比,评价肺水肿情况;通过实时荧光定量反转录⁃聚合酶链反应检测促凝及纤溶相关指标组织因子(TF)和纤溶酶 原激活物抑制剂⁃1(PAI⁃1)的mRNA 表达;通过蛋白质免疫印迹实验检测TF、PAI⁃1蛋白表达及NF⁃κB 通路 相关蛋白 p⁃p65、p65、p⁃IKKβ、IKKβ 的活性表达。结果 与对照组比较,LPS 组肺泡壁增厚、结构破坏;肺 泡间隔明显增宽、炎症细胞浸润增多 ;肺损伤评分明显升高;肺水肿明显加重。肺组织中 TF、PAI⁃1 的 mRNA 水平明显升高;同时组肺组织 TF、PAI⁃1、p⁃p65 及 p⁃IKKβ 的蛋白表达水平均明显增加。与 LPS 组比较,不同剂量姜辣素组大鼠肺泡壁增厚及结构破坏相对减少,肺泡间隔增宽程度减轻,肺组织炎症细胞浸 润减少,肺损伤评分及湿/干比明显下降 ;肺组织中 TF、PAI⁃1 的 mRNA 水平及蛋白表达水平均降低,同时肺组织中 p65 与 p⁃IKKβ 的蛋白表达水平下降,且呈剂量依耐性降低。结论 姜辣素能剂量依耐性改善 LPS 诱导 ARDS 大鼠肺泡凝血和纤溶抑制的状态,有效减轻肺组织损伤,其机制可能与抑制 NF⁃κB 信号通路活化有关。 

关键词: 姜辣素, 急性呼吸窘迫综合征, NF?κB 信号通路, 凝血, 纤溶

Abstract:

Objective To explore the preventive and therapeutic effects of gingerol on lipopolysaccharide (LPS)⁃ induced procoagulant and fibrinolytic inhibition in acute respiratory distress syndrome(ARDS)rats and its possible mechanism. Methods Male SD rats were randomly divided into control group,LPS group and different dose of gingerol group(10 m/kg,20 m/kg,30 m/kg). The ARDS model of rats was induced by LPS intratracheal atomization inhalation and treated by intraperitoneal injection of different doses of gingerol. The pathological changes of rat lung were observed by H&E staining,and the degree of lung injury was evaluated. The wet/dry ratio of lung tissue was calculated to evaluate pulmonary edema;the mRNA expression of tissue factor(TF),and plasminogen activator inhibitor⁃1(PAI⁃1) was detected by real⁃time fluorescence quantitative reverse transcription polymerase chain reaction;western blot was used to detect the protein expressions of TF,PAI⁃1 and nuclear factor⁃ κB p65(p65),phosphorylation of p65(p⁃p65),inhibitor of nuclear factor⁃κB kinase(IKKβ)and phos⁃ phorylation of IKKβ(p⁃IKKβ)in lung tissues. Results Compared with those in the control group,the pulmonary tissues in the model group were seen with damaged alveolar structures,widened alveolar septa,increased inflam⁃ matory cell infiltration and increased lung injury score. The mRNA level of TF and PAI⁃1 in lung tissue was signifi⁃ cantly increased,and the protein expression level of TF,PAI⁃1,p65 and IKK in lung tissue of group A was signifi⁃ cantly increased. Compared to those in the model group,lung tissues in mice of gingerol groups were seen with decreased deconstruction,narrowed alveolar septa,decreased inflammtory cells infiltration and declined lung injury score. In gingerol groups,pulmonary expressions of TF,PAI⁃1,p⁃p65,and p⁃IKKβ protein were all decreased or declined,among which the changes of above indexes in mice with high dose gingerol were more obvious than those in mice with medium and low dose. Conclusion Gingerol dose⁃dependently ameliorates alveolar hypercoagulation and fibrinolytic inhibition and reduces lung injury for LPS⁃induced ARDS in rat,and the effects might be associated with the inactivation of NF⁃ κ B signal pathway. 

Key words: gingerol, acute respiratory distress syndrome, nuclear factor?κB, coagulation, fibri? nolysis