治疗肺纤维化方药对PM2.5致大鼠肺损伤的保护作用
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摘要
目的:评价治疗肺纤维化方药(扶正通络消积三方:养清抗纤方、保肺化纤方、金水缓纤方)对PM2.5致肺损伤大鼠炎性反应、氧化应激及胶原沉积的影响。方法:50只雄性SD大鼠随机分为对照组、模型组、养清抗纤组、保肺化纤组、金水缓纤组。大气PM2.5实时浓缩进行动物暴露。自暴露第1天起,对照组、模型组给予0.9%氯化钠溶液,治疗组给予相应中药灌胃14d,至第15天取材,检测大鼠肺功能,观察肺组织病理,检测肺组织羟脯氨酸(HYP)含量、肺脏局部炎性反应、氧化应激水平。结果:与对照组比较,模型组大鼠肺功能显著降低(P<0.01),血清T-AOC显著降低、MDA水平显著升高(P<0.01),肺组织TNF-α、IL-6、IL-1β、MBP、ELA2表达水平,及HYP含量、胶原沉积显著增加(P<0.05,P<0.01);养清抗纤方、保肺化纤方及金水缓纤方均能改善上述指标变化,其中养清抗纤方在改善肺功能,减轻肺组织病理损伤,及升高T-AOC、降低MDA,降低肺组织TNF-α、IL-6、 IL-1β、 MBP、ELA2的表达各作用机制方面均优于其余两方。结论:PM2.5暴露可增加肺组织胶原沉积,引起病理形态损伤,其中炎性反应和氧化-抗氧化失衡在此过程发挥重要作用;扶正通络消积三方可有效改善PM2.5暴露致肺损伤的炎性反应和氧化应激,减轻肺组织损伤,其中以养清抗纤方作用尤为显著。
Objective: To evaluate the effect of pulmonary fibrosis-treatment formulae(Yangqing Kangxian Formula,Baofei Huaxian Formula, Jinshui Huanxian Formula) on inflammation, oxidative stress and collagen deposition in lung injury rats induced by particulate matter(PM) 2.5. Methods: Fifty SD rats were randomly divided into control group, model group, Yangqing Kangxian group, Baofei Huaxian group and Jinshui Huanxian group. Real-time atmospheric concentrated PM2.5 was used to establish rats model. Since the first day exposed with PM2.5, rats in control and model groups were gavaged with 0.9% sodium chloride solution, while rats in treatment groups were gavaged with corresponding traditional Chinese medicine respectively for fourteen days. Rats were sacrificed at fifteen day of exposure, pulmonary function, histomorphology, hydroxyproline content,inflammation and oxidative stress levels were measured respectively. Results: Compared with control group, pulmonary function in model group was significantly lower(P<0.01). Serum total antioxidant capacity(T-AOC) decreased, whereas malonaldehyde(MDA) increased(P<0.01). The expressions of tumor necrosis factor(TNF)-α, interleukin-6(IL-6), interleukin-1β(IL-1β),myelin basic protein(MBP), elastase 2(ELA2), as well as the levels of hydroxyproline, collagen deposition in lung tissues increased(P<0.05, P<0.01). Yangqing Kangxian Formula, Baofei Huaxian Formula and Jinshui Huanxian Formula can improve these indexes mentioned above, in which Yangqing Kangxian Formula showed better effects than the other two formulae. Conclusion:PM2.5 exposure can lead to lung injury in histomorphology and an increase in collagen deposition. Inflammation and oxidative/antioxidative imbalance play an important role in such progress. All of these three Fuzheng Tongluo Xiaoji Formulae can alleviate lung injury induced by PM2.5 by regulating inflammation and oxidative stress, especially Yangqing Kangxian Formula.
Objective: To evaluate the effect of pulmonary fibrosis-treatment formulae(Yangqing Kangxian Formula,Baofei Huaxian Formula, Jinshui Huanxian Formula) on inflammation, oxidative stress and collagen deposition in lung injury rats induced by particulate matter(PM) 2.5. Methods: Fifty SD rats were randomly divided into control group, model group, Yangqing Kangxian group, Baofei Huaxian group and Jinshui Huanxian group. Real-time atmospheric concentrated PM2.5 was used to establish rats model. Since the first day exposed with PM2.5, rats in control and model groups were gavaged with 0.9% sodium chloride solution, while rats in treatment groups were gavaged with corresponding traditional Chinese medicine respectively for fourteen days. Rats were sacrificed at fifteen day of exposure, pulmonary function, histomorphology, hydroxyproline content,inflammation and oxidative stress levels were measured respectively. Results: Compared with control group, pulmonary function in model group was significantly lower(P<0.01). Serum total antioxidant capacity(T-AOC) decreased, whereas malonaldehyde(MDA) increased(P<0.01). The expressions of tumor necrosis factor(TNF)-α, interleukin-6(IL-6), interleukin-1β(IL-1β),myelin basic protein(MBP), elastase 2(ELA2), as well as the levels of hydroxyproline, collagen deposition in lung tissues increased(P<0.05, P<0.01). Yangqing Kangxian Formula, Baofei Huaxian Formula and Jinshui Huanxian Formula can improve these indexes mentioned above, in which Yangqing Kangxian Formula showed better effects than the other two formulae. Conclusion:PM2.5 exposure can lead to lung injury in histomorphology and an increase in collagen deposition. Inflammation and oxidative/antioxidative imbalance play an important role in such progress. All of these three Fuzheng Tongluo Xiaoji Formulae can alleviate lung injury induced by PM2.5 by regulating inflammation and oxidative stress, especially Yangqing Kangxian Formula.
引文
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[14]Kerri A Johannson,Eric Vittinghoff,Kiyoung Lee,et al.Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure.Eur Respir J,2014,43(4):1124-1131
[15]Kamata H,Tasaka S,Inoue K,et al.Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice.Exp Biol Med(Maywood),2011,236(3):315-324
[16]Li R,Zhou R,Zhang J.Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases.Oncol Lett,2018,15(5):7506-7514
[17]Falcon-Rodriguez C I,Osornio-Vargas A R,Sada-Ovalle I,et al.Aero particles,composition,and lung diseases.Front Immunol,2016,7:3
[18]田燕歌,李亚,李建生,等.PM2.5影响呼吸系统疾病的机制探讨.中医学报,2014,29(12):1721-1723
[19]Cachon B F,Firmin S,Verdin A,et al.Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter(PM(2.5)and PM(>2.5))collected from Cotonou,Benin.Environ Pollut,2014,185:340-351
[20]Snow S J,De Vizcaya-Ruiz A,Osornio-Vargas A,et al.The effect of composition,size,and solubility on acute pulmonary injury in rats following exposure to Mexico City ambient particulate matter samples.J Toxicol Environ Health A,2014,77(19):1164-1182
[21]Steenhof M,Gosens I,Strak M,et al.In vitro toxicity of particulate matter(PM)collected at different sites in the Netherlands is associated with PM composition,size fraction and oxidative potential-the RAPTES project.Part Fibre Toxicol, 2011,8:26
[22]Hu Y,Wang L S,Li Y,et al.Effects of particulate matter from straw burning on lung fibrosis in mice.Environ Toxicol Pharmacol,2017,56:249-258
[23]姜良铎,秦英.试论“环境毒”.中国中医基础医学杂志,1999,5(9):4-6
[24]秦玉英,刘颖,敬岳,等.PM2.5对呼吸系统的病理影响及中医药防治.中华中医药杂志,2015,30(10):3477-3482
[2]Winterbottom C J,Shah R J,Patterson K C,et al.Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathicpulmonary fibrosis.Chest,2018,153(5):1221-1228
[3]SeséL,Nunes H,Cottin V,et al.Role of atmospheric pollution on the natural history of idiopathic pulmonary fibrosis.Thorax,2018,73(2):145-150
[4]Byrne J D,Baugh J A.The significance of nanoparticles in particleinduced pulmonary fibrosis.Mcgill J Med,2008,11(1):43-50
[5]Kamata H,Tasaka S,Inoue K-I,et al.Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice.Exp Biol Med,2011,236(3):315-324
[6]李建生,宋建平.正虚络痹积损为弥漫性间质性肺疾病的主要病机.中医杂志,2013,54(1):23-25
[7]李建生.特发性肺纤维化中医辨证治疗概要.中医学报,2017,32(6):929-931
[8]白云苹,赵栋梁,王明航,等.弥漫性间质性肺疾病中医基础证候的文献研究.中华中医药杂志,2011,26(2):277-281
[9]中华中医药学会肺系病专业委员会.弥漫性间质性肺疾病的中医证候诊断标准(2012版).中医杂志,2012,53(13):1163-1165
[10]李萌.基于调控IKK/IκB/NF-κB信号通路的扶正通络消积三方治疗肺纤维化疗效及远后效应机制.北京:北京中医药大学,2017
[11]黄继汉,黄晓辉,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算.中国临床药理学与治疗学,2004,9(9):1069-1072
[12]Shi T,Knaapen A M,Begerow J,et al.Temporal variation of hydroxyl radical generation and 8-hydroxy-2'-deoxyguanosine formation by coarse and fine particulate matter.Occup Environ Med,2003,60(5):315-321
[13]Avalos A,Haza A I,Mateo D,et al.Effects of silver and gold nanoparticles of different sizes in human pulmonary fibroblasts.Toxicol Mech Methods,2015,25(4):1-9
[14]Kerri A Johannson,Eric Vittinghoff,Kiyoung Lee,et al.Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure.Eur Respir J,2014,43(4):1124-1131
[15]Kamata H,Tasaka S,Inoue K,et al.Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice.Exp Biol Med(Maywood),2011,236(3):315-324
[16]Li R,Zhou R,Zhang J.Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases.Oncol Lett,2018,15(5):7506-7514
[17]Falcon-Rodriguez C I,Osornio-Vargas A R,Sada-Ovalle I,et al.Aero particles,composition,and lung diseases.Front Immunol,2016,7:3
[18]田燕歌,李亚,李建生,等.PM2.5影响呼吸系统疾病的机制探讨.中医学报,2014,29(12):1721-1723
[19]Cachon B F,Firmin S,Verdin A,et al.Proinflammatory effects and oxidative stress within human bronchial epithelial cells exposed to atmospheric particulate matter(PM(2.5)and PM(>2.5))collected from Cotonou,Benin.Environ Pollut,2014,185:340-351
[20]Snow S J,De Vizcaya-Ruiz A,Osornio-Vargas A,et al.The effect of composition,size,and solubility on acute pulmonary injury in rats following exposure to Mexico City ambient particulate matter samples.J Toxicol Environ Health A,2014,77(19):1164-1182
[21]Steenhof M,Gosens I,Strak M,et al.In vitro toxicity of particulate matter(PM)collected at different sites in the Netherlands is associated with PM composition,size fraction and oxidative potential-the RAPTES project.Part Fibre Toxicol, 2011,8:26
[22]Hu Y,Wang L S,Li Y,et al.Effects of particulate matter from straw burning on lung fibrosis in mice.Environ Toxicol Pharmacol,2017,56:249-258
[23]姜良铎,秦英.试论“环境毒”.中国中医基础医学杂志,1999,5(9):4-6
[24]秦玉英,刘颖,敬岳,等.PM2.5对呼吸系统的病理影响及中医药防治.中华中医药杂志,2015,30(10):3477-3482