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基于TLR-4/NF-κB信号通路及水通道蛋白1表达探讨大陷胸汤干预重症急性胰腺炎早期肺损伤的效应机制
王天麟,曲鹏飞,高万朋,张真,贺燕丽,杨朝帅,王红
天津中医药大学第二附属医院天津 300150
摘要:
目的 探讨大陷胸汤对重症急性胰腺炎(SAP)早期肺损伤的影响及作用机制。方法:将60只大鼠随机分为实验组、模型组和对照组,每组20只。实验组予大陷胸汤灌胃,对照组及模型组予蒸馏水灌胃,在连续灌胃7 d后,模型组与实验组以胰胆管注射牛黄胆酸钠的方式制备SAP模型,于造模后12、24、48、72 h各时间点分别处死5只大鼠取材,观察大鼠一般情况、胸腹水量、肺湿干比重、胰腺组织及肺组织病理学改变、肺组织白细胞介素(IL)-1及Toll样受体4(TLR-4)水平、肺组织核因子(NF)-κB及水通道蛋白1(AQP1)表达水平。结果:与对照组相比,模型组大鼠一般情况较差,胰腺炎症反应以及肺损伤程度较重,胸腹水量、肺湿干比重、肺组织NF-κB表达水平、IL-1及TLR-4水平升高(P<0.05),肺组织AQP1表达水平下降。与模型组相比,实验组大鼠一般情况较好,肺损伤程度较轻,胸腹水量、肺湿干比重、肺组织NF-κB表达水平、IL-1及TLR-4水平下降(P<0.05),肺组织AQP1表达水平升高,造模后72 h后,胰腺组织坏死程度与同期模型组相比明显好转。结论:大陷胸汤可在一定程度上减轻SAP大鼠早期肺损伤,其机制可能与抑制TLR-4/NF-κB炎症信号通路,增强AQP1表达有关。
关键词:  重症急性胰腺炎  急性肺损伤  大陷胸汤  Toll样受体4/核因子-κB信号通路  水通道蛋白1
DOI:10.3969/j.issn.1007-6948.2023.02.019
基金项目:国家自然科学基金青年项目(81202780);天津市教< 委科研计划项目(2018KJ016);天津市卫生健康委中医中西医结合科研项目(2019075)
Based on TLR-4/NF-κB signaling pathway and AQP1 expression to explore the effector mechanism of intervention of Daxianxiong decoction on early lung injury in severe acute pancreatitis
WANG Tian-lin,QU Peng-fei,GAO Wan-peng
Department of Emergency, the Second Affiliated Hospital of Tianjin University of TCM, Tianjin300150, China
Abstract:
Objective To investigate the effects and the underlying mechanism of lung injury in the early stage of severe acute pancreatitis treated with daxianxiong decoction. Methods a total of 60 rats were randomly divided into experimental, model, and control groups, with 20 rats in each group. The rats in the experimental group were intragastrically administrated with daxianxiong decoction, the control group and the model group were intragastrically administered with distilled water, and after 7 days of continuous gavage, the model group and the experimental group were treated with sodium taurocholate by pancreatobiliary injection to prepare the sap model. At each time point of 12 h, 24 h, 48 h, and 72 h after the model, five rats were sacrificed and the general condition, thoracic and abdominal water volumes, lung wet and dry specific weights, pancreatic and lung histopathological changes, lung IL-1 and TLR-4 levels, and lung NF-κB and AQP1 expression levels. Results compared with the control group, the rats in the model group were in poor general condition, and had more severe pancreatic inflammatory reaction as well as lung injury, thoracic and abdominal water volumes, lung wet and dry specific weights, and lung tissue NF-κB, the levels of IL-1 and TLR-4 were increased (P<0.05), while AQP1 expression was decreased in lung tissue. Compared with the model group, the rats in the experimental group generally had better general condition and less severe lung injury, as indicated by the lower amount of thoracic and abdominal water, lung wet and dry specific weights, and the NF-κB of lung tissue expression levels, IL-1 and TLR-4 levels were decreased (P<0.05), AQP1 expression levels were increased in lung tissue, and the degree of necrosis in pancreatic tissue at 72 h after modeling was significantly improved compared with the same period model group. Conclusion the early lung injury in SAP rats was alleviated by Daxianxiong Decoction to some extent, and the mechanism may be related to the inhibition of TLR-4/NF-κB inflammatory signaling pathways that enhance AQP1 expression are involved.
Key words:  Severe acute pancreatitis  acute lung injury  Daxianxiong decoction  TLR-4/NF-κB signaling pathways  AQP1

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