| 引用本文: | 马琳,张萌,陈光宴.基于TGF-β1/Smads信号通路观察异丙托溴铵雾化液对慢性阻塞性肺疾病大鼠肺功能、气道重塑的影响[J].中国现代应用药学,2022,39(24):3249-3255. |
| MA Lin,ZHANG Meng,CHEN Guangyan.Effects of Ipratropium Bromide Atomizing Liquid on Lung Function and Airway Remodeling in Rats with Chronic Obstructive Pulmonary Disease via TGF-β1/Smads Signaling Pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(24):3249-3255. |
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| 基于TGF-β1/Smads信号通路观察异丙托溴铵雾化液对慢性阻塞性肺疾病大鼠肺功能、气道重塑的影响 |
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马琳1, 张萌1, 陈光宴2
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1.山东中医药大学第二附属医院职业病科, 济南 250001;2.兖矿新里程总医院呼吸科, 山东 济宁 273500
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| 摘要: |
| 目的 研究异丙托溴铵雾化液对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠肺功能、气道重塑的影响及其对于转化生长因子β1(transforming growth factor-β1,TGF-β1)/母体抗生物皮肤生长因子同源物2/3 (mothers against decapentaplegic homolog 2/3,Smad2/3)通路信号通路的调控机制。方法 将SD大鼠按照随机数字表法分为正常组、模型组、实验组、阳性对照组,每组15只;其中模型组、实验组、阳性对照组中的大鼠以泰山茉莉香烟烟熏法复制COPD大鼠模型:将大鼠放入烟熏箱内,点燃15只泰山茉莉香烟,持续1 h,每日3次,连续90 d,正常组大鼠不进行烟熏操作,常规喂养。成功复制COPD模型后,实验组大鼠每日在自制微小动物密闭箱内以雾化器吸入用异丙托溴铵溶液1 mg/4 mL,每日1次,每次2 h,阳性对照组大鼠皮下注射TGF-β1抑制剂LY2157299(20 mg·kg-1),每日1次,正常组、模型组大鼠分别皮下注射等剂量的生理盐水。在给药28 d后,使用小微动物肺功能测定仪依次检测各组大鼠的肺功能。TUNEL染色各组大鼠肺组织中的细胞凋亡,免疫荧光检测各组大鼠肺组织中气道重塑标志蛋白α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达,Western blotting检测各组大鼠肺组织中TGF-β1、p-Smad2/3的表达。结果 与正常组相比,模型组大鼠的呼吸频率、肺组织的细胞凋亡率、α-SMA的荧光强度、TGF-β1、p-Smad2/3的表达出现了明显升高,大鼠的通气量和潮气量出现了明显下降(均P<0.05);与模型组相比,实验组和阳性对照组大鼠的呼吸频率、肺组织的细胞凋亡率、α-SMA的荧光强度、TGF-β1、p-Smad2/3的表达出现了明显下降,大鼠的通气量和潮气量出现了明显升高(均P<0.05)。结论 异丙托溴铵能抑制肺组织的细胞凋亡,缓解COPD大鼠的气道重塑,改善其肺功能,这可能与抑制TGF-β1/Smads通路有关。 |
| 关键词: 异丙托溴铵雾化液 慢性阻塞性肺疾病 肺功能 气道重塑 转化生长因子β1/母体抗生物皮肤生长因子同源物2/3信号通路 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.24.009 |
| 分类号:R285.5 |
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| Effects of Ipratropium Bromide Atomizing Liquid on Lung Function and Airway Remodeling in Rats with Chronic Obstructive Pulmonary Disease via TGF-β1/Smads Signaling Pathway |
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MA Lin1, ZHANG Meng1, CHEN Guangyan2
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1.Department of Occupational Diseases, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China;2.Department of Respiratory, Yankuang New Journey General Hospital, Jinin 273500, China
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| Abstract: |
| OBJECTIVE To explore effects of ipratropium bromide atomizing liquid on lung function and airway remodeling in rats with chronic obstructive pulmonary disease(COPD) and its regulation on transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 2/3(Smad 2/3) signaling pathway. METHODS According to the random number table method, the SD rats were divided into normal group, model group, experimental group, and positive control group, each with 15 rats. The rats in the model group, experimental group and positive control group were smoked with Taishan jasmine cigarettes method to replicate the COPD rat model:the rats were put into a smoking box, 15 Taishan jasmine cigarettes were lightened for 1 h, 3 times a day for 90 consecutive days. The rats in the normal group do not smoke. After successfully replicating the COPD model, rats in the experimental group inhaled ipratropium bromide solution 1 mg/4 mL with a nebulizer in a self-made small animal airtight box, once a day for 2 h each time, rats in the positive control group were injected subcutaneously with TGF-β1 inhibitor LY2157299(20 mg·kg-1), once a day, rats in the normal group and model group were injected subcutaneously with equal doses of normal saline. After 28 days of administration, the pulmonary function of each group of rats was sequentially tested using a small and micro animal pulmonary function tester. TUNEL staining was used to detect the apoptosis in the lung tissues of rats in each group, and immunofluorescence was used to detect the expression of the airway remodeling marker protein α-smooth muscle actin(α-SMA) in the lung tissues of the rats in each group. Western blotting was used to detect the expression of TGF-β1 and p-Smad2/3 in the lung tissues of rats in each group. RESULTS Compared with the normal group, the respiratory rate, the apoptosis rate of lung tissue, the fluorescence intensity of α-SMA, the expression of TGF-β1 and p-Smad2/3 in the model group appeared a significant increase(all P<0.05), the rat's ventilation and tidal volume appeared a significant decreased (all P<0.05). Compared with the model group, the respiratory rate, the apoptosis rate of lung tissue, the fluorescence intensity of α-SMA, the expression of TGF-β1 and p-Smad2/3 in the experimental group and the positive control group appeared significantly decreased(all P<0.05), and the rats' ventilation and tidal volume appeared increased significantly(all P<0.05). CONCLUSION Ipratropium bromide can inhibit lung cell apoptosis, relieve airway remodeling in COPD rats, and improve lung function. This may be related to the inhibition of TGF-β1/Smads pathway. |
| Key words: ipratropium bromide atomizing liquid chronic obstructive pulmonary disease lung function airway remodeling transforming growth factor-β1(TGF-β1)/mothers against decapentaplegic homolog 2/3(Smad2/3) signaling pathway |
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