Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease.

Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease.
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三种调补肺肾疗法对慢性阻塞性肺疾病大鼠 NF-κB/TGF-β1/smad2 信号传导的长期影响

DOI:
10.1186/1472-6882-14-140
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发表时间:
2014-04-26
影响因子:
--
通讯作者:
Wang Y
Wang Y
中科院分区:
医学3区
文献类型:
--
作者:
Li Y;Li JS;Li WW;Li SY;Tian YG;Lu XF;Jiang SL;Wang Y

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背景调补肺肾颗粒(补肺健脾颗粒、补肺益肾颗粒、益气滋肾颗粒)在减少慢性阻塞性肺疾病(COPD)患者急性发作次数、缩短急性发作时间、改善中医证候、改善肺功能、提高运动能力等方面具有良好的临床疗效。但其短期或长期机制尚不完全清楚。核因子(NF)-κB/转化生长因子(TGF)-β1/smad 2信号通路参与慢性阻塞性肺疾病(COPD)炎症和肺重构的发生发展。方法SD大鼠随机分为正常对照组、模型组、补肺健脾组、补肺益肾组、益气滋肾组和氨茶碱组,每组10只。采用香烟烟雾和细菌感染诱导的COPD大鼠模型,于第9 ~ 20周分别灌胃生理盐水、补肺健脾、补肺益肾、益气滋肾颗粒和氨茶碱。在第20周和第32周,收获肺组织。采用免疫组化法检测白细胞介素(IL)1 β和肿瘤坏死因子(TNF)α的表达,实时定量聚合酶链反应(qRT-PCR)检测TGF β1和Smad 2的mRNA表达,Western blotting检测NF κB(p-NF-κB)和IκBα(p-IκBα)的磷酸化水平。在三种中药治疗的动物中均有所改善。COPD大鼠肺组织中IL-1β、TNF-α、p-NF-κB、p-IκBα、TGF-β1和Smad 2水平均显著高于对照组,而中药组和氨茶碱组肺组织中IL-1β、TNF-α、p-NF-κ B、p-IκBα、TGF-β1和Smad 2水平均显著低于对照组。与氨茶碱组比较,补肺健脾组和补肺益肾组各项指标均明显降低,且差异有统计学意义。与20周比较,治疗32周时3个中药组的各项指标均显著下降。结论3种调补肺神法均能减轻COPD患者的肺部炎症和重塑,且具有显著的远期疗效。NF-κB/TGF-β1/smad 2信号通路可能参与了这一机制。
BackgroundThe three Tiao-Bu Fei-Shen (Bufei Jianpi, Bufei Yishen, Yiqi Zishen) granules have been confirmed for their beneficial clinical efficacy in chronic obstructive pulmonary disease (COPD) patients on reducing frequency and duration of acute exacerbation, improving syndromes, pulmonary function and exercise capacity. But the short- or long-term mechanism of them is not fully clear. Nuclear factor (NF)-κB/transforming growth factor (TGF)-β1/smad2 signaling pathway is involved in the progress of inflammation and remodeling in chronic obstructive pulmonary disease COPD. This study aimed to explore the long-term effects mechanism of Tiao-Bu Fei-Shen granules by regulating NF-κB/TGF-β/Smads signaling in rats with COPD.MethodsSprague Dawley rats were randomized into control, model, Bufei Jianpi, Bufei Yishen, Yiqi Zishen and aminophylline groups. COPD rats, induced by cigarette smoke and bacterial infections exposures, were administrated intragastricly by normal saline, Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or aminophylline from week 9 through 20, respectively. At week 20 and 32, lung tissues were harvested. Immunohistochemistry was used to detect interleukin (IL)-1β and tumor necrosis factor (TNF)-α, quantitative real-time polymerase chain reaction (qRT-PCR) was used for TGF-β1 and Smad2 mRNA analysis, western blotting was used to determine the phosphorylation of NF-κB (p-NF-κB) and IκBα (p-IκBα).ResultsCOPD rats had marked airway injury, such as chronic airway inflammation and remodeling, emphysema, which were improved in the three traditional Chinese medicines (TCM)-treated animals. The levels of IL-1β, TNF-α, p-NF-κB, p-IκBα, TGF-β1 and Smad2 were significantly higher in COPD rats than in controls, while they were dramatically reduced in the three TCM- and aminophylline-treated groups. At the meantime, all these endpoints were significantly lower in three TCM-treated groups than in aminophylline group, especially in Bufei Jianpi and Bufei Yishen groups. Compared to week 20, all endpoints decreased significantly in three TCM groups at week 32.ConclusionThe three Tiao-Bu Fei-Shen therapies can reduce pulmonary inflammation and remodeling in COPD and have significant long-term effects. NF-κB/TGF-β1/smad2 signaling might be involved in the mechanism.
DOI: 10.1186/1472-6882-12-197
发表时间: 2012-10-29
影响因子: --
作者:
Li SY;Li JS;Wang MH;Xie Y;Yu XQ;Sun ZK;Ma LJ;Zhang W;Zhang HL;Cao F;Pan YC
通讯作者: Pan YC
DOI: 10.1378/chest.121.5_suppl.188s
发表时间: 2002-05-01
期刊: CHEST
影响因子: 9.6
作者:
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通讯作者: Churg, A
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发表时间: 2010-10-01
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发表时间: 2005-01-01
期刊: Proceedings of the American Thoracic Society
影响因子: --
作者:
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通讯作者: Chung, Kian Fan
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发表时间: 2012-01-01
影响因子: 15.9
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