艾灸对类风湿性关节炎患者血清中VEGF、IL-1β影响的研究
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摘要
目的:观察艾灸对类风湿性关节炎(RA)患者血清中血管内皮生长因子(VEGF)及白细胞介素-1β(IL-1β)含量的影响,探讨艾灸治疗RA起效的作用机制。方法:符合本研究纳入标准的门诊及住院共40例患者,随机分为艾灸组、对照组各20例,对照组采用西药甲氨蝶呤或来氟米特治疗,艾灸组在对照组的基础上配合艾灸"足三里""肾俞""阿是穴",治疗前后分别对RA患者的临床症状、实验室指标、关节疾病活动度评分(DAS28评分)和血清中VEGF、IL-1β的含量进行比较。结果:(1)两组患者治疗后临床症状及实验室指标皆有改善(P<0.01),但艾灸组对压痛指数及实验室指标的改善更显著(P<0.01)。(2)两组患者治疗后血清中VEGF、IL-1β的含量均有下降(P<0.01),但艾灸组患者血清中VEGF、IL-1β含量下降更为显著(P<0.01,P<0.05)。结论:艾灸增强了西药对RA患者血清中VEGF、IL-1β含量和临床症状的改善,可能是艾灸治疗RA的起效机制之一。
Objective:To observe the clinical effects of moxibustion on vascular endothelial growth factor(VEGF) and interleukin-1β(IL-1β) in the serum in rheumatoid arthritis(RA) patients for revealing the underlying mechanism of moxibustion in the treatment of RA patients. Methods: This study selected 40 patients from both inpatient population and outpatients clinics, all patients fulfilled the inclusion criteria and were randomly assigned to the control and moxibustion groups in equal ratio(20 patients per group). The control group was treated with Methotrexate or Leflunomide and the moxibustion group was treated with Methotrexate or Leflunomide and moxibustion at Zusanli(ST36), Shenshu(BL23) and Ashi point. Before and after treatment,the patients' clinical symptoms, DAS28 scores and laboratory findings, including serum VEGF and IL-1β levels were recorded for further comparison. Results:(1)Two groups' clinical symptoms and laboratory parameters after treatment were improved(P<0.01), but the moxibustion group's pain index and laboratory indicators improved more than those of the control group(P<0.01).(2)After treatment, the VEGF and IL-1 β in serum were decreased in treatment and control groups(P<0.01).While compared with the control group, those in moxibustion group decreased considerably(P<0.01). Conclusion: Moxibustion enhanced the effect of routine western medicine on VEGF and IL-1β levels in serum in RA patients and improved the clinical symptoms,which may be one of the effective mechanisms of moxibustion treatment for RA.
Objective:To observe the clinical effects of moxibustion on vascular endothelial growth factor(VEGF) and interleukin-1β(IL-1β) in the serum in rheumatoid arthritis(RA) patients for revealing the underlying mechanism of moxibustion in the treatment of RA patients. Methods: This study selected 40 patients from both inpatient population and outpatients clinics, all patients fulfilled the inclusion criteria and were randomly assigned to the control and moxibustion groups in equal ratio(20 patients per group). The control group was treated with Methotrexate or Leflunomide and the moxibustion group was treated with Methotrexate or Leflunomide and moxibustion at Zusanli(ST36), Shenshu(BL23) and Ashi point. Before and after treatment,the patients' clinical symptoms, DAS28 scores and laboratory findings, including serum VEGF and IL-1β levels were recorded for further comparison. Results:(1)Two groups' clinical symptoms and laboratory parameters after treatment were improved(P<0.01), but the moxibustion group's pain index and laboratory indicators improved more than those of the control group(P<0.01).(2)After treatment, the VEGF and IL-1 β in serum were decreased in treatment and control groups(P<0.01).While compared with the control group, those in moxibustion group decreased considerably(P<0.01). Conclusion: Moxibustion enhanced the effect of routine western medicine on VEGF and IL-1β levels in serum in RA patients and improved the clinical symptoms,which may be one of the effective mechanisms of moxibustion treatment for RA.
引文
[1] Kormendy D, Hoff H, Hoff P, et al. Impact of the CTLA-4/cd28 axis on the processes of joint inflammation in rheumatoid arthritis[J]. Arthritis Rheum, 2013, 65(1): 81-87.
[2] Ciciriello S, Buchbinder R, Osborne RH, et al. Improving treatment with methotrexate in rheumatoid arthritis Development of a multimedia patient education program and the Mi RAK,a new instrument to evaluate methotrexate-related knowledge[C]. Seminars in arthritis and rheumatism, 2014, 43(4): 437-446.
[3] 殷媛, 陈天帷, 张瑞, 等. 艾灸对胶原诱导性关节炎大鼠血清白介素-17和肿瘤坏死因子α含量的影响[J]. 针刺研究,2017,42(2): 149-152.
[4] 张传英, 邵芙蓉, 蔡荣林, 等. 艾灸对类风湿性关节炎大鼠关节滑膜组织转录信号转导因子1、细胞因子信号负调控因子基因表达的影响[J]. 针刺研究, 2015, 40(3):205-209.
[5] Funovits J, Aletaha D, Bykerk V, et al.The 2010 American College of Rheumatology/European League Against Rheumatism classifi cation criteria for rheumatoid arthritis: methodological report phase I[J].Ann Rheum Dis, 2010, 69(9):1589-1595.
[6] Aletaha D, Neogi T, Silman AJ, et al.2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J].Ann Rheum Dis, 2010, 69(9):1580-1588.
[7] 郑筱萸. 中药新药临床研究指导原则(试行)[S].北京:中国医药科技出版社社,2002:115-119.
[8] Michael Yellin, Igor Paliienko, Andra Balanescu, et al. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of MDX-1100, a Fully Human Anti-CXCL10 Monoclonal Antibody, in Combination With Methotrexate in Patients With Rheumatoid Arthritis[J]. ARTHRITIS & RHEUMATISM , 2012, 64(6):1730-1739.
[9] 达古拉, 李鸿斌.VEGF在类风湿性关节炎血管形成中的作用及其相关研究进展[J].医学综述,2012,18(5):644-648.
[10] Kigure W, Fujii T, Sutoh T, et al. The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor[J]. Hepato-gastroenterology, 2013, 60(122): 277-280.
[11] Paradowska-Gorycka A, Pawlik A, Romanowska-Prochnicka K, et al. Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis[J]. PLOS ONE, 2016, 11(8): e0160769.
[12] Noh EM, Kim JS, Hur H, et al. cordycepin inhibits 1L-1 beta induced mmp-1 and mmp-3 expression in rheumatoid arthritis synovial fibroblasts[J].Rheumatology (Oxford), 2009,48 (1) :45-48.
[13] Darrieutort-Laffite C, Boutet MA, Chatelais M, et al. IL-1 beta and TNF-alpha promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts [J].Mediators lnflamm, 2014,17:241840.
[14] 蔡辉, 张群燕, 郭郡浩, 等. 类风湿关节炎患者外周血血浆中TNF-α、IL-1β及IL-10的表达及临床意义[J]. 中华中医药学刊, 2017,35(3):519-521.
[15] 欧阳八四, 高洁, 车建丽, 等. 电针对活动性类风湿关节炎患者外周血与关节滑液中TNF-α与VEGF的影响[J]. 中华中医药杂志, 2012,27(2): 504-506.
[16] Shuang FU, Gao X, Yang XS, et al. Effects of Voltaren on the Changes of VEGF and TNF-α in Patients with Rheumatoid Arthritis and its Clinical Curative Effect[J]. Progress in Modern Biomedicine, 2016, 16(14): 2744-2748.
[17] 陈白露, 彭麒, 熊燕, 等. 艾灸对实验性RA家兔滑膜HIF-1α/VEGF的调节作用[J]. 时珍国医国药,2016, 27(12):3042-3044.
[18] JH Chung, H Lee, J Kim. Reduction of interleukin-1β induced matrix metalloproteinase-3 release by extracts of six plants: inhibitory screening of 35 traditional medicinal plants[J]. Immunopharmacology and Immunotoxicology, 2011, 33(3): 461-465.
[19] 李建武, 刘建民. 隔物温和灸联合甲氨蝶呤对RA模型大鼠关节肿胀及IL-1β、TNF-α的影响[J]. 上海针灸杂志, 2008, 27(11):32-34.
[20] 杨慎峭, 刘旭光, 余曙光, 等. 艾灸对类风湿性关节炎家兔关节滑膜液IL-1β、TNF-α含量的影响[J]. 成都中医药大学学报, 2005, 28(3):11-12.
[21] 俞红五,朱艳. 艾灸辅助治疗类风湿关节炎患者临床疗效观察及机制探讨[J]. 中国针灸,2016, 36(1): 17-20.
[22] 陈白露, 彭麒, 周玉梅, 等. 肾俞,足三里,阳陵泉在类风湿关节炎治疗中的作用探讨[J]. 辽宁中医杂志,2015, 42(6):1315.
[23] Yao J, Ling HU, Song XG, et al. Influence of moxibustion at“Shenshu”( BL 23) and “Zusanli”( ST 36) on Ras-MAPK signal pathways in synovial tissues of rats with experimental rheumatoid arthritis[J]. World Journal of Acupuncture-Moxibustion, 2013, 23(2):29-33.
[2] Ciciriello S, Buchbinder R, Osborne RH, et al. Improving treatment with methotrexate in rheumatoid arthritis Development of a multimedia patient education program and the Mi RAK,a new instrument to evaluate methotrexate-related knowledge[C]. Seminars in arthritis and rheumatism, 2014, 43(4): 437-446.
[3] 殷媛, 陈天帷, 张瑞, 等. 艾灸对胶原诱导性关节炎大鼠血清白介素-17和肿瘤坏死因子α含量的影响[J]. 针刺研究,2017,42(2): 149-152.
[4] 张传英, 邵芙蓉, 蔡荣林, 等. 艾灸对类风湿性关节炎大鼠关节滑膜组织转录信号转导因子1、细胞因子信号负调控因子基因表达的影响[J]. 针刺研究, 2015, 40(3):205-209.
[5] Funovits J, Aletaha D, Bykerk V, et al.The 2010 American College of Rheumatology/European League Against Rheumatism classifi cation criteria for rheumatoid arthritis: methodological report phase I[J].Ann Rheum Dis, 2010, 69(9):1589-1595.
[6] Aletaha D, Neogi T, Silman AJ, et al.2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J].Ann Rheum Dis, 2010, 69(9):1580-1588.
[7] 郑筱萸. 中药新药临床研究指导原则(试行)[S].北京:中国医药科技出版社社,2002:115-119.
[8] Michael Yellin, Igor Paliienko, Andra Balanescu, et al. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of MDX-1100, a Fully Human Anti-CXCL10 Monoclonal Antibody, in Combination With Methotrexate in Patients With Rheumatoid Arthritis[J]. ARTHRITIS & RHEUMATISM , 2012, 64(6):1730-1739.
[9] 达古拉, 李鸿斌.VEGF在类风湿性关节炎血管形成中的作用及其相关研究进展[J].医学综述,2012,18(5):644-648.
[10] Kigure W, Fujii T, Sutoh T, et al. The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor[J]. Hepato-gastroenterology, 2013, 60(122): 277-280.
[11] Paradowska-Gorycka A, Pawlik A, Romanowska-Prochnicka K, et al. Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis[J]. PLOS ONE, 2016, 11(8): e0160769.
[12] Noh EM, Kim JS, Hur H, et al. cordycepin inhibits 1L-1 beta induced mmp-1 and mmp-3 expression in rheumatoid arthritis synovial fibroblasts[J].Rheumatology (Oxford), 2009,48 (1) :45-48.
[13] Darrieutort-Laffite C, Boutet MA, Chatelais M, et al. IL-1 beta and TNF-alpha promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts [J].Mediators lnflamm, 2014,17:241840.
[14] 蔡辉, 张群燕, 郭郡浩, 等. 类风湿关节炎患者外周血血浆中TNF-α、IL-1β及IL-10的表达及临床意义[J]. 中华中医药学刊, 2017,35(3):519-521.
[15] 欧阳八四, 高洁, 车建丽, 等. 电针对活动性类风湿关节炎患者外周血与关节滑液中TNF-α与VEGF的影响[J]. 中华中医药杂志, 2012,27(2): 504-506.
[16] Shuang FU, Gao X, Yang XS, et al. Effects of Voltaren on the Changes of VEGF and TNF-α in Patients with Rheumatoid Arthritis and its Clinical Curative Effect[J]. Progress in Modern Biomedicine, 2016, 16(14): 2744-2748.
[17] 陈白露, 彭麒, 熊燕, 等. 艾灸对实验性RA家兔滑膜HIF-1α/VEGF的调节作用[J]. 时珍国医国药,2016, 27(12):3042-3044.
[18] JH Chung, H Lee, J Kim. Reduction of interleukin-1β induced matrix metalloproteinase-3 release by extracts of six plants: inhibitory screening of 35 traditional medicinal plants[J]. Immunopharmacology and Immunotoxicology, 2011, 33(3): 461-465.
[19] 李建武, 刘建民. 隔物温和灸联合甲氨蝶呤对RA模型大鼠关节肿胀及IL-1β、TNF-α的影响[J]. 上海针灸杂志, 2008, 27(11):32-34.
[20] 杨慎峭, 刘旭光, 余曙光, 等. 艾灸对类风湿性关节炎家兔关节滑膜液IL-1β、TNF-α含量的影响[J]. 成都中医药大学学报, 2005, 28(3):11-12.
[21] 俞红五,朱艳. 艾灸辅助治疗类风湿关节炎患者临床疗效观察及机制探讨[J]. 中国针灸,2016, 36(1): 17-20.
[22] 陈白露, 彭麒, 周玉梅, 等. 肾俞,足三里,阳陵泉在类风湿关节炎治疗中的作用探讨[J]. 辽宁中医杂志,2015, 42(6):1315.
[23] Yao J, Ling HU, Song XG, et al. Influence of moxibustion at“Shenshu”( BL 23) and “Zusanli”( ST 36) on Ras-MAPK signal pathways in synovial tissues of rats with experimental rheumatoid arthritis[J]. World Journal of Acupuncture-Moxibustion, 2013, 23(2):29-33.