补肺健脾方调控TNF-α/TNFR/NF-κB通路对COPD大鼠骨骼肌炎性反应的影响
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摘要
目的:评价补肺健脾方调控TNF-α/TNFR/NF-κB通路对慢性阻塞性肺疾病(COPD)大鼠骨骼肌炎性反应的影响。方法:SD大鼠60只随机分为对照组、模型组、补肺健脾组、NF-κB抑制剂组(PDTC组)、补肺健脾+PDTC组(联合组)和氨茶碱组,采用香烟暴露联合细菌感染法制作COPD稳定期模型后,于第9-20周分别给予相应药物。采用QPCR和Western blot技术观察股四头肌、肋间肌、肱二头肌和比目鱼肌组织中TNF-α、TNFR和NF-κB的表达。结果:模型组4种肌肉TNF-α、TNFR、NF-κB基因和蛋白表达水平均较对照组显著升高(P<0.01),补肺健脾方可不同程度的改善上述指标(P<0.05,P<0.01),其中联合组改善明显,疗效优于氨茶碱。结论:补肺健脾方可以显著改善COPD大鼠骨骼肌萎缩,其机制可能与TNF-α/TNFR/NF-κB通路改善骨骼肌炎性反应有关。
Objective: To observe the effects of Bufei Jianpi Formula on skeletal muscular inflammation via TNF-α/TNFR/NF-κB pathway in rats with chronic obstructive pulmonary disease(COPD). Methods: 60 SD rats were randomly divided into control group, model group, Bufei Jianpi group, PDTC(Ammonium pyrrolidinedithiocarbamate, nuclear factor(NF)-κBselective inhibitor) group, Bufei Jianpi + PDTC group and aminophylline group. The stable COPD rat model was established by cigarette smoke inhalation combined with bacterial infection, and the drug administration was performed by gavage from the 9 th week to 20 th week respectively. The expressions of TNF-α, TNFR and NF-κB in quadriceps, intercostal, biceps and soleus muscles were detected by q PCR and western blotting. Results: The expressions of TNF-α, TNFR and NF-κB markedly increased in the 4 kinds of striated muscles in COPD rats(P<0.01), and the above indicators could be improved to varying degrees by Bufei Jianpi Formula(P<0.05, P<0.01). The combination of PDTC and Bufei Jianpi Formula had more powerful effect on reducing TNF-α, TNFR and NF-κB, which was better than that of the aminophylline group. Conclusion: Bufei Jianpi Formula could improve skeletal muscle function in COPD rats via improving TNF-α, TNFR and NF-κB expressions.
Objective: To observe the effects of Bufei Jianpi Formula on skeletal muscular inflammation via TNF-α/TNFR/NF-κB pathway in rats with chronic obstructive pulmonary disease(COPD). Methods: 60 SD rats were randomly divided into control group, model group, Bufei Jianpi group, PDTC(Ammonium pyrrolidinedithiocarbamate, nuclear factor(NF)-κBselective inhibitor) group, Bufei Jianpi + PDTC group and aminophylline group. The stable COPD rat model was established by cigarette smoke inhalation combined with bacterial infection, and the drug administration was performed by gavage from the 9 th week to 20 th week respectively. The expressions of TNF-α, TNFR and NF-κB in quadriceps, intercostal, biceps and soleus muscles were detected by q PCR and western blotting. Results: The expressions of TNF-α, TNFR and NF-κB markedly increased in the 4 kinds of striated muscles in COPD rats(P<0.01), and the above indicators could be improved to varying degrees by Bufei Jianpi Formula(P<0.05, P<0.01). The combination of PDTC and Bufei Jianpi Formula had more powerful effect on reducing TNF-α, TNFR and NF-κB, which was better than that of the aminophylline group. Conclusion: Bufei Jianpi Formula could improve skeletal muscle function in COPD rats via improving TNF-α, TNFR and NF-κB expressions.
引文
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[22]Chen Z J.Ubiquitin signalling in the NF-κB pathway.Nat Cell Biol,2005,7(8):758-765
[23]Kumar A,Takada Y,Boriek A M,et al.Nuclear factor-kappa B:its role in health and disease.J Mol Med,2004,829(7):434-448
[24]Messina S,Bitto A,Aguennouz M,et al.Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice.Exp Neurol,2006,198:234-241
[2]Taivassalo T,Hussain S N.Contribution of the Mitochondria to Locomotor Muscle Dysfunction in Patients With COPD.Chest,2016,149(5):1302-1312
[3]Barreiro E.Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions.Proteomes,2016,4(2):18
[4]Ceco E,Weinberg S E,Chandel N S,et al.Metabolism and skeletal muscle homeostasis in lung disease.Am J Respir Cell Mol Biol,2017,57(1):28-34
[5]Balasubramanian V P,Varkey B.Chronic obstructive pulmonary disease:effects beyond the lungs.Curr Opin Pulm Med,2006,12(2):106-112
[6]Maltais F,Decramer M,Casaburi R,et al.An official American Thoracic Society/European Respiratory Society statement:update on limbmuscle dysfunction in chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2014,189(9):15-62
[7]Langen R C,Haegens A,Vernooy J H,et al.NF-k B activation is required for the transitionof pulmonary inflammation to muscle atrophy.Am J Respir Cell Mol Biol,2012,47(3):288-297
[8]Li Y,Li S Y,Li J S,et al.A rat model for stable chronic obstructive pulmonary disease induced by cigarette smoke inhalation and repetitive bacterial infection.Biol Pharm Bull,2012,35(10):1752-1760
[9]李素云,李亚,李建生,等.补肺健脾方对慢性阻塞性肺疾病大鼠膈神经放电和膈肌功能的影响.中国中西医结合杂志,2012,32(6):812-816
[10]中华中医药学会内科分会肺系病专业委员会.慢性阻塞性肺疾病中医证候诊断标准(2011版).中医杂志,2012,53(2):177-178
[11]中华中医药学会内科分会肺系病专业委员会.慢性阻塞性肺疾病中医诊疗指南(2011版).中医杂志,2012,53(1):80-84
[12]段永强,成映霞,梁玉杰,等.益气健脾中药对脾虚大鼠骨骼肌组织中Ca2+/Ca MKⅡ通路关键分子的干预作用.中药材,2015,38(3):562-566
[13]许淑芬,方颖,穆立新.加味补中益气汤合经皮电刺激干预下肢肌肉萎缩的疗效观察.中药药理与临床,2015,31(1):322-323
[14]徐升.黄芪建中汤对慢性阻塞性肺疾病稳定期患者呼吸肌疲劳的影响.中国中医急症,2011,20(1):31-33
[15]Li S Y,Li J S,Wang M H,et al.Effects of comprehensive therapy based on traditional Chinese medicine patterns in stable chronic obstructive pulmonary disease:a four-center,openlabel,randomized,controlled study.BMC Complement Altern Med,2012,12:197
[16]李素云,李亚,李建生,等.调补肺肾三法治疗慢性阻塞性肺疾病大鼠疗效及远后效应.中华中医药杂志,2012,27(12):3116-3121
[17]李建生,李亚,李素云,等.调补肺肾三法对慢性阻塞性肺疾病稳定期大鼠模型全身和肺脏炎症反应的影响及远期效应(英文).中西医结合学报,2012,10(9):1039-1048
[18]Li Y,Li J S,Li W W,et al.Long-term effects of three Tiao-Bu FeiShen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease.BMC Complement Altern Med,2014,14:140
[19]Li J,Yang L,Yao Q,et al.Effects and mechanism of bufeiyishen formula in a rat chronic obstructive pulmonary disease model.Evid Based Complement Alternat Med,2014,381976
[20]Dong Y,Li Y,Sun Y,et al.Bufei Jianpi granules improve skeletal muscle and mitochondrial dysfunction in rats with chronic obstructive pulmonary disease.BMC Complementary and Alternative Medicine,2015,15:51
[21]Yanbaeva D G,Dentener M A,Creutzberg E C,et al.Systemic inflammation in COPD:is genetic susceptibility a key factor.COPD,2006,3(1):51-61
[22]Chen Z J.Ubiquitin signalling in the NF-κB pathway.Nat Cell Biol,2005,7(8):758-765
[23]Kumar A,Takada Y,Boriek A M,et al.Nuclear factor-kappa B:its role in health and disease.J Mol Med,2004,829(7):434-448
[24]Messina S,Bitto A,Aguennouz M,et al.Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice.Exp Neurol,2006,198:234-241