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通过PI3K/Akt/NF-κB信号通路减轻香烟烟雾介导的慢性阻塞性肺疾病(COPD)大鼠模型的气道重塑

Attenuates Airway Remodeling via PI3K/Akt/NF-B Pathway in Cigarette Smoke Mediated-COPD Rats Model.

作者信息

Xu Fei, Lin Jinpei, Cui Wenqiang, Kong Qing, Li Qiuping, Li Lulu, Wei Ying, Dong Jingcheng

机构信息

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Institutes of Integrative Medicine, Fudan University, Shanghai, China.

出版信息

Evid Based Complement Alternat Med. 2018 May 13;2018:1281420. doi: 10.1155/2018/1281420. eCollection 2018.

DOI:10.1155/2018/1281420
PMID:29861765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5971322/
Abstract

(SB) is commonly used in traditional Chinese medicine for chronic inflammatory diseases. This study aims to investigate the effects of the early intervention with SB on airway remodeling in a well-established rat model of COPD induced by cigarette smoking. COPD model in Sprague Dawley (SD) rats were established by exposing them to smoke for 6 days/week, for 12 weeks, 24 weeks, or 36 weeks. Meanwhile, rats were randomly divided into normal control group, model group, Budesonide (BUD) group, and the SB (low, middle, and high) dose groups with 8 rats in each group and 3 stages (12 weeks, 24 weeks, and 36 weeks). After treatment, the pulmonary function was evaluated by BUXCO system and the morphology changes of the lungs were observed with HE and Masson staining. The serum IL-6, IL-8, and IL-10 and TNF-, TGF-beta (TGF-1), MMP-2, MMP-9, and TIMP-1 levels in BALF were detected by ELISA-kit assay. The protein expression levels of AKT and NF-B (p65) were determined by western blot (WB). The oral of SB significantly improved pulmonary function (PF) and ameliorated the pathological damage and attenuated inflammatory cytokines infiltration into the lungs. Meanwhile, the levels of TGF-, MMP-2, MMP-9, and TIMP-1 were partially significantly decreased. The levels of PI3K/AKT/NF-B pathway were also markedly suppressed by SB. SB could significantly improve the condition of airway remodeling by inhibiting airway inflammation and partially quenching TGF- and MMPs via PI3K/AKT/NF-B pathway.

摘要

(SB)常用于中医治疗慢性炎症性疾病。本研究旨在探讨在已建立的吸烟诱导的慢性阻塞性肺疾病(COPD)大鼠模型中,早期使用SB干预对气道重塑的影响。通过每周6天、持续12周、24周或36周暴露于烟雾中,建立Sprague Dawley(SD)大鼠的COPD模型。同时,将大鼠随机分为正常对照组、模型组、布地奈德(BUD)组和SB(低、中、高)剂量组,每组8只大鼠,共3个阶段(12周、24周和36周)。治疗后,通过BUXCO系统评估肺功能,并用HE和Masson染色观察肺的形态变化。采用ELISA试剂盒检测血清IL-6、IL-8、IL-10以及BALF中TNF-α、TGF-β(TGF-1)、MMP-2、MMP-9和TIMP-1水平。通过蛋白质印迹法(WB)测定AKT和NF-κB(p65)的蛋白表达水平。口服SB可显著改善肺功能(PF),减轻病理损伤,减少炎症细胞因子浸润到肺中。同时,TGF-β、MMP-2、MMP-9和TIMP-1水平部分显著降低。SB还显著抑制PI3K/AKT/NF-κB信号通路水平。SB可通过抑制气道炎症,并通过PI3K/AKT/NF-κB信号通路部分抑制TGF-β和基质金属蛋白酶,显著改善气道重塑状况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/4e28258bec4c/ECAM2018-1281420.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/1ecb41949cf9/ECAM2018-1281420.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/4f68d8c5e744/ECAM2018-1281420.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/eaa276742dcf/ECAM2018-1281420.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/16a9ea92e749/ECAM2018-1281420.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/605c2b9a62b8/ECAM2018-1281420.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/a43d84d100f7/ECAM2018-1281420.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/0e6567c37283/ECAM2018-1281420.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/4e28258bec4c/ECAM2018-1281420.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/1ecb41949cf9/ECAM2018-1281420.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/4f68d8c5e744/ECAM2018-1281420.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/eaa276742dcf/ECAM2018-1281420.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/16a9ea92e749/ECAM2018-1281420.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/605c2b9a62b8/ECAM2018-1281420.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/a43d84d100f7/ECAM2018-1281420.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/0e6567c37283/ECAM2018-1281420.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/947c/5971322/4e28258bec4c/ECAM2018-1281420.008.jpg

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