清气化痰丸加减治疗慢性阻塞性肺疾病急性加重期的临床疗效及对患者炎性反应、气道重塑和血栓形成机制的影响
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摘要
目的:观察清气化痰丸加减治疗慢性阻塞性肺疾病(COPD)急性加重期(AECOPD)的临床疗效及对患者炎性反应、气道重塑和血栓形成机制的影响。方法:将80例患者按随机数字表法分为对照组与治疗组,各40例,对照组给予西医常规治疗,治疗组在对照组基础上加服清气化痰丸加减治疗,两组疗程均为14 d。比较两组患者治疗前后中医证候积分,COPD和支气管哮喘生理评分(CAPS),COPD患者自我评估测试问卷(CAT),肺功能及血气分析,血清核转录因子-κB(NF-κB),白细胞介素-6(IL-6),白细胞介素-8(IL-8),基质金属蛋白酶-2(MMP-2),金属蛋白酶组织抑制剂-2(TIMP-2),转化生长因子-β_1(TGF-β_1)和血浆组织型纤溶酶原激活剂(t-PA),纤溶酶原激活物抑制剂(PAI-1),血管性血友病因子(v-WF)水平,临床疗效和安全性指标。结果:治疗组临床疗效总有效率为94. 74%,对照组78. 38%,治疗组优于对照组(χ~2=4. 341,P <0. 05)。两组治疗后中医证候积分,CAPS,CAT,二氧化碳分压(PaCO_2),血清NF-κB,IL-6,IL-8,MMP-2,TIMP-2,TGF-β_1水平和血浆PAI-1,v-WF水平与本组治疗前比较均降低(P <0. 05);两组治疗后第1秒用力呼气容积(FEV_1),第1秒用力呼气容积占预计值百分比(FEV_1%),第1秒用力呼气容积占用力肺活量的百分比(FEV_1/FVC),血氧饱和度(SaO_2),血氧分压(PaO_2),血浆t-PA与本组治疗前比较均升高(P <0. 05);且治疗组改善优于对照组(P <0. 05)。结论:清气化痰丸加减治疗AECOPD疗效确切且安全,能够改善患者CAPS评分和肺功能,有效的抑制患者炎性反应、气道重塑和血栓形成,分析其机制可能是通过降低炎症细胞因子水平,调节MMP-2/TIMP-2和t-PA/PAI-1动态平衡起作用,改善细胞外基质和血管内皮功能,保护肺组织。
Objective: To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method: A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) were randomly divided into control group( 40 cases) and therapy group( 40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group,the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine( TCM) syndrome,chronic obstructive pulmonary disease and asthma physiology Score( CAPS),and chronic obstructive pulmonary disease patients self-assessment test questionnaire( CAT) were compared. The secondary indicators were pulmonary function,arterial blood gas analysis,and blood rheology indexes. In addition,the levels of serum nuclear factor kappa B( NF-κB),interleukin-6( IL-6), interleukin-8( IL-8), matrix metalloproteinase-2( MMP-2), tissue inhibitor of metalloproteinase-2( TIMP-2), transforming growth factor-beta1( TGF-β_1) and plasma tissue-plasminogen activator( t-PA),plasminogen activator inhibitor-1( PAI-1),von-willebrand factor( v-WF),clinical efficacy and safety were evaluated. Result: The total clinical effective rate was 94. 74% in therapy group,which was higher than 78. 38% in control group( χ~2= 4. 341,P < 0. 05). After treatment,scores of TCM syndrome,CAPS,CAT and levels of PaCO_2,serum NF-κB,IL-6,IL-8,MMP-2,TIMP-2,TGF-β_1 and plasma PAI-1,v-WF in therapy group were lower than those in control group( P < 0. 05). However,levels of plasma t-PA,SaO_2,PaO_2,FEV_1,FEV_1%,FEV_1/FVC in therapy group were higher than those in control group( P < 0. 05),therapy group was alleviated more than control group( P < 0. 05). Conclusion: Modified Qingqi Huatan Wan can control the symptoms safely,alleviate CAPS and lung function,effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis,and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.
Objective: To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method: A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) were randomly divided into control group( 40 cases) and therapy group( 40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group,the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine( TCM) syndrome,chronic obstructive pulmonary disease and asthma physiology Score( CAPS),and chronic obstructive pulmonary disease patients self-assessment test questionnaire( CAT) were compared. The secondary indicators were pulmonary function,arterial blood gas analysis,and blood rheology indexes. In addition,the levels of serum nuclear factor kappa B( NF-κB),interleukin-6( IL-6), interleukin-8( IL-8), matrix metalloproteinase-2( MMP-2), tissue inhibitor of metalloproteinase-2( TIMP-2), transforming growth factor-beta1( TGF-β_1) and plasma tissue-plasminogen activator( t-PA),plasminogen activator inhibitor-1( PAI-1),von-willebrand factor( v-WF),clinical efficacy and safety were evaluated. Result: The total clinical effective rate was 94. 74% in therapy group,which was higher than 78. 38% in control group( χ~2= 4. 341,P < 0. 05). After treatment,scores of TCM syndrome,CAPS,CAT and levels of PaCO_2,serum NF-κB,IL-6,IL-8,MMP-2,TIMP-2,TGF-β_1 and plasma PAI-1,v-WF in therapy group were lower than those in control group( P < 0. 05). However,levels of plasma t-PA,SaO_2,PaO_2,FEV_1,FEV_1%,FEV_1/FVC in therapy group were higher than those in control group( P < 0. 05),therapy group was alleviated more than control group( P < 0. 05). Conclusion: Modified Qingqi Huatan Wan can control the symptoms safely,alleviate CAPS and lung function,effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis,and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.
引文
[1]马蕴蕾,宿英豪,于向艳.补肾益肺化纤方治疗慢性阻塞性肺疾病稳定期合并肺纤维化疗效及对患者肺功能及生活质量的影响[J].中国实验方剂学杂志,2018,24(11):168-172.
[2] Vogelmeier C F,Criner G J,Martinez F J,et al. Global strategy for the diagnosis,management,and prevention of chronic obstructive lung disease 2017 report:GOLD executive summary[J]. Am J Respir Crit Care Med,2017,195(5):557-582.
[3] DU J,CHI Y,SONG Z,et al. Crocin reduces aspergillus fumigatus-induced airway inflammation and NF-κB signal activation[J]. J Cell Biochem,2018,119(2):1746-1754.
[4]黄少君,傅汝梅.培土生金方对慢性阻塞性肺疾病稳定期患者气道重塑机制的观察[J].中国实验方剂学杂志,2018,24(1):174-179.
[5] Hosokawa K,Ohnishi-Wada T,Sameshima-Kaneko H,et al. Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by increasing thrombolysis resistance under shear stress in an in-vitro flow chamber model[J]. Thromb Res,2016,146(1):69-75.
[6]张文斌,雷文汇,冯英凯.竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病[J].中国实验方剂学杂志,2017,23(11):190-195.
[7]王胜,叶海勇,陈悦,等. 302例慢性阻塞性肺疾病急性加重期中医证候分型[J].北京中医药大学学报,2015,38(1):57-62.
[8]李建生,张海龙,王海峰,等.慢性阻塞性肺疾病证候演变特点临床调查[J].中医杂志,2017,58(9):772-776.
[9]方明,张国庆.清气化痰汤加减联合西医治疗急性期COPD疗效观察及对血清INF-γ、TGF-α的影响[J].中药材,2018,41(4):992-994.
[10]慢性阻塞性肺疾病急性加重(AECOPD)诊治专家组.慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2017年更新版)[J].国际呼吸杂志,2017,37(14):1041-1057.
[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证候诊断标准(2011版)[J].中医杂志,2012,53(2):177-178.
[12]中华人民共和国卫生部.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:54-58.
[13]吴珂,尚立芝,谢文英,等.二陈汤加味对慢性阻塞性肺疾病细支气管壁细胞外基质重塑的影响[J].中国实验方剂学杂志,2018,24(14):122-127.
[14] WANG H,YANG T,WEN F,et al. Elevated circulating PAI-1 levels are related to lung function decline,systemic inflammation,and small airway obstruction in chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2016,11(1):2369-2376.
[15]张玉溪.芩丹汤对慢性阻塞性肺疾病急性加重期患者血清炎性因子及血浆纤维蛋白原的影响[J].中国实验方剂学杂志,2016,22(12):172-176.
[16] LIU X, YIN S, ZHAO P, et al. LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-κB,STAT3 or AP-1 activation[J]. Molecul Med Rep,2018,17(4):5484-5491.
[17] ZHANG J,LI Q,SHAO Q,et al. Effects of Panax notoginseng saponin on the pathological ultrastructure and serum IL-6 and IL-8 in pulmonary fibrosis in rabbits[J]. J Cell Biochem,2018,22(10):1097-4644.
[18] Martinez B K,White C M. The emerging role of inflammation in cardiovascular disease[J]. Ann Pharmacother,2018,52(8):801-809.
[19] LO C,HUANG H,WANG C,et al. Increased matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio in smokers with airway hyperresponsiveness and accelerated lung function decline[J]. Int J Chron Obstruct Pulmon Dis,2018,13(11):1135-1144.
[20] Vitenberga Z, Pilmane M. Age-related lung tissue remodeling due to the local distribution of MMP-2,TIMP-2,TGF-βand Hsp70[J]. Biotech Histochem,2018,93(4):239-248.
[21] Drzewiecka-Jdrzejczyk M,WlazeR,Terlecka M,et al.Serum metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in lung carcinoma patients[J]. J Thorac Dis,2017,9(12):5306-5313.
[22] YANG Y C,ZHANG N,Van Crombruggen K,et al.Transforming growth factor-beta1 in inflammatory airway disease:a key for un-derstanding inflammation and remodeling[J]. Allergy,2012,67(10):1193-1202.
[23]唐婷玉,俞李羚,陆晓玲,等.活血化瘀治疗对慢性阻塞性肺疾病伴高凝状态患者血管内皮功能的影响[J].中华中医药学刊,2015,33(9):2192-2194.
[24] Ozolina A,Sarkele M,Sabelnikovs O,et al. Activation of coagulation and fibrinolysis in acute respiratory distress syndrome:a prospective pilot study[J]. Front Med:Lausanne,2016,doi:10. 3389/fmed. 2016. 00064.
[25] George R,Sivadasanpillai H, Jayakumari N,et al.Circulating thrombotic risk factors in young patients with coronary artery disease who are on statins and antiplatelet drugs[J]. Indian J Clin Biochem,2016,31(3):302-309.
[26] Bártholo T P,Costa C H,Rufino R E,et al. Valuation of von-Willebrand factor in COPD patients[J]. J Bras Pneumol,2014,40(4):373-379.
[2] Vogelmeier C F,Criner G J,Martinez F J,et al. Global strategy for the diagnosis,management,and prevention of chronic obstructive lung disease 2017 report:GOLD executive summary[J]. Am J Respir Crit Care Med,2017,195(5):557-582.
[3] DU J,CHI Y,SONG Z,et al. Crocin reduces aspergillus fumigatus-induced airway inflammation and NF-κB signal activation[J]. J Cell Biochem,2018,119(2):1746-1754.
[4]黄少君,傅汝梅.培土生金方对慢性阻塞性肺疾病稳定期患者气道重塑机制的观察[J].中国实验方剂学杂志,2018,24(1):174-179.
[5] Hosokawa K,Ohnishi-Wada T,Sameshima-Kaneko H,et al. Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by increasing thrombolysis resistance under shear stress in an in-vitro flow chamber model[J]. Thromb Res,2016,146(1):69-75.
[6]张文斌,雷文汇,冯英凯.竹叶石膏汤合清气化痰丸加减治疗急性加重期慢性阻塞性肺疾病[J].中国实验方剂学杂志,2017,23(11):190-195.
[7]王胜,叶海勇,陈悦,等. 302例慢性阻塞性肺疾病急性加重期中医证候分型[J].北京中医药大学学报,2015,38(1):57-62.
[8]李建生,张海龙,王海峰,等.慢性阻塞性肺疾病证候演变特点临床调查[J].中医杂志,2017,58(9):772-776.
[9]方明,张国庆.清气化痰汤加减联合西医治疗急性期COPD疗效观察及对血清INF-γ、TGF-α的影响[J].中药材,2018,41(4):992-994.
[10]慢性阻塞性肺疾病急性加重(AECOPD)诊治专家组.慢性阻塞性肺疾病急性加重(AECOPD)诊治中国专家共识(2017年更新版)[J].国际呼吸杂志,2017,37(14):1041-1057.
[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证候诊断标准(2011版)[J].中医杂志,2012,53(2):177-178.
[12]中华人民共和国卫生部.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002:54-58.
[13]吴珂,尚立芝,谢文英,等.二陈汤加味对慢性阻塞性肺疾病细支气管壁细胞外基质重塑的影响[J].中国实验方剂学杂志,2018,24(14):122-127.
[14] WANG H,YANG T,WEN F,et al. Elevated circulating PAI-1 levels are related to lung function decline,systemic inflammation,and small airway obstruction in chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2016,11(1):2369-2376.
[15]张玉溪.芩丹汤对慢性阻塞性肺疾病急性加重期患者血清炎性因子及血浆纤维蛋白原的影响[J].中国实验方剂学杂志,2016,22(12):172-176.
[16] LIU X, YIN S, ZHAO P, et al. LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-κB,STAT3 or AP-1 activation[J]. Molecul Med Rep,2018,17(4):5484-5491.
[17] ZHANG J,LI Q,SHAO Q,et al. Effects of Panax notoginseng saponin on the pathological ultrastructure and serum IL-6 and IL-8 in pulmonary fibrosis in rabbits[J]. J Cell Biochem,2018,22(10):1097-4644.
[18] Martinez B K,White C M. The emerging role of inflammation in cardiovascular disease[J]. Ann Pharmacother,2018,52(8):801-809.
[19] LO C,HUANG H,WANG C,et al. Increased matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio in smokers with airway hyperresponsiveness and accelerated lung function decline[J]. Int J Chron Obstruct Pulmon Dis,2018,13(11):1135-1144.
[20] Vitenberga Z, Pilmane M. Age-related lung tissue remodeling due to the local distribution of MMP-2,TIMP-2,TGF-βand Hsp70[J]. Biotech Histochem,2018,93(4):239-248.
[21] Drzewiecka-Jdrzejczyk M,WlazeR,Terlecka M,et al.Serum metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in lung carcinoma patients[J]. J Thorac Dis,2017,9(12):5306-5313.
[22] YANG Y C,ZHANG N,Van Crombruggen K,et al.Transforming growth factor-beta1 in inflammatory airway disease:a key for un-derstanding inflammation and remodeling[J]. Allergy,2012,67(10):1193-1202.
[23]唐婷玉,俞李羚,陆晓玲,等.活血化瘀治疗对慢性阻塞性肺疾病伴高凝状态患者血管内皮功能的影响[J].中华中医药学刊,2015,33(9):2192-2194.
[24] Ozolina A,Sarkele M,Sabelnikovs O,et al. Activation of coagulation and fibrinolysis in acute respiratory distress syndrome:a prospective pilot study[J]. Front Med:Lausanne,2016,doi:10. 3389/fmed. 2016. 00064.
[25] George R,Sivadasanpillai H, Jayakumari N,et al.Circulating thrombotic risk factors in young patients with coronary artery disease who are on statins and antiplatelet drugs[J]. Indian J Clin Biochem,2016,31(3):302-309.
[26] Bártholo T P,Costa C H,Rufino R E,et al. Valuation of von-Willebrand factor in COPD patients[J]. J Bras Pneumol,2014,40(4):373-379.