程氏蠲痹汤加减方对风寒湿型佐剂关节炎大鼠影响
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摘要
目的 :观察程氏蠲痹汤加减方(CJBD)对风寒湿型佐剂关节炎(AA)大鼠的体质量、多发性关节炎指数(AI)、双侧足趾容积及血清中白介素-6(IL-6)与白介素-10(IL-10)的影响。方法 :除正常组的大鼠,其余均复制成风寒湿型AA大鼠模型,分为模型组,甲氨蝶呤(MTX)组,CJBD高、中、低剂量组。评估CJBD对实验大鼠治疗前后的体质量、多发性关节炎指数、双侧足趾容积的影响,酶联免疫吸附(ELISA)法检测大鼠血清中IL-6、IL-10的水平。结果 :治疗后发现,模型组的体质量均低于MTX组,CJBD高、中、低剂量组(P<0.05);CJBD、MTX治疗的大鼠AI评分明显下降(P<0.05);和模型组相比,MTX组和CJBD高、中、低剂量组的双侧足趾容积明显减小(P<0.05);与模型组比,MTX组,CJBD高、中、低剂量组的IL-6表达水平明显降低,IL-10明显升高(P<0.05)。结论:不同剂量的CJBD均使风寒湿型AA大鼠的体质量减轻得到缓解,AI评分减小,达到缓解双侧足趾肿胀的作用;抑制血清中IL-6的分泌,上调IL-10的水平,且对剂量有依赖性。
Objective :To investigate the effects of modified Cheng's Juanbi Decoction(CJBD)on the weight,arthritis index(AI),toes on both sides of the volume and serum interleukin 6(IL-6)and interleukin 10(IL-10)among rats with adjuvant arthritis(AA). Methods :In addition to the normal group of rats,and the rest were copied the wind cold dampness type AA rats model,divided into model group,methotrexate(MTX)group,the CJBD high,medium and low dose group. Assessed the influence of CJBD in experimental rats before and after treatment of the weight,AI and the toes on both sides of the volume;Enzyme-linked immunosorbent(ELISA)method to detect the rat serum IL-6,IL-10 levels. Results :After treatment,found that the weight of model group were lower than that of MTX group,CJBD high,medium and low dose group(P<0.05);CJBD,MTX treatment of AI score significantly decreased in rats(P<0.05);Compared with model group,MTX group and CJBD high,medium and low dose groups on both sides of the toes on both sides of the volume significantly decreased(P<0.05);Than with the model group,MTX group,the CJBD high,medium and low dose group of IL-6 expression level decreased obviously,IL-10 increased significantly(P<0.05). Conclusion :Different doses of CJBD can reduce the wind cold dampness type AA rat body weight,reduce AI grading,ease bilateral toes swelling;Inhibit the secretion of IL-6 in serum,increase the level of IL-10,and is dose-dependent.
Objective :To investigate the effects of modified Cheng's Juanbi Decoction(CJBD)on the weight,arthritis index(AI),toes on both sides of the volume and serum interleukin 6(IL-6)and interleukin 10(IL-10)among rats with adjuvant arthritis(AA). Methods :In addition to the normal group of rats,and the rest were copied the wind cold dampness type AA rats model,divided into model group,methotrexate(MTX)group,the CJBD high,medium and low dose group. Assessed the influence of CJBD in experimental rats before and after treatment of the weight,AI and the toes on both sides of the volume;Enzyme-linked immunosorbent(ELISA)method to detect the rat serum IL-6,IL-10 levels. Results :After treatment,found that the weight of model group were lower than that of MTX group,CJBD high,medium and low dose group(P<0.05);CJBD,MTX treatment of AI score significantly decreased in rats(P<0.05);Compared with model group,MTX group and CJBD high,medium and low dose groups on both sides of the toes on both sides of the volume significantly decreased(P<0.05);Than with the model group,MTX group,the CJBD high,medium and low dose group of IL-6 expression level decreased obviously,IL-10 increased significantly(P<0.05). Conclusion :Different doses of CJBD can reduce the wind cold dampness type AA rat body weight,reduce AI grading,ease bilateral toes swelling;Inhibit the secretion of IL-6 in serum,increase the level of IL-10,and is dose-dependent.
引文
[1]葛均波,徐永健.内科学[M].8版.北京:人民卫生出版社,2013:808.
[2]Chemin K,Klareskog L,Malmstrom V. Is rheumatoid arthritis an autoimmune disease[J]. Curr Opin Rheumatol,2016,28(2):181-188.
[3]Terao C,Ikari K,Nakayamada S,et al. A twin study of rheumatoid arthritis in the Japanese population[J]. Mod Rheumatol,2016,26(5):685-689.
[4]Neumann E,Frommer K,Diller M,et al. Rheumatoid arthritis[J].Zeitschrift fur Rheumatologie,2018,77(9):769-775.
[5]Zhang A,Lee YC. Mechanisms for Joint Pain in Rheumatoid Arthritis(RA):from Cytokines to Central Sensitization[J].Current Osteoporosis Reports,2018,16(5):603-610.
[6]王冰,高明利.四神煎治疗气阴两虚型类风湿关节炎的研究进展[J].风湿病与关节炎,2018,7(6):76-80.
[7]Tank ND,Karelia BN,Vegada BN. Biological Response Modifiers in Rheumatoid Arthritis:Systematic Review and Meta-analysis of Safety[J]. J Pharmacol Pharmacother,2017,8(3):92-105.
[8]Ishiguro N,Dougados M,Cai Z,et al. Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis:Post hocanalyses of overall and Japanese results from two phase 3 clinical trials[J]. Mod Rheumatol,2018,28(6):1-10.
[9]姜泉,王海隆,巩勋,等.类风湿关节炎病证结合诊疗指南[J].中医杂志,2018,59(20):1794-1800.
[10]许霞,杜欢,程卉,等.程氏蠲痹汤加减方含药血清对佐剂性关节炎大鼠外周血单核细胞TNF-α和IL-1β表达的影响[J].安徽中医药大学学报,2016,35(6):83-86.
[11]许霞,程卉,曹健,等.程氏蠲痹汤加减方降低佐剂关节炎大鼠滑膜组织前列腺素E受体4(PTGER4)的水平[J].细胞与分子免疫学杂志,2017,33(6):736-740.
[12]许霞,杜欢,吴亚兰,等.程氏蠲痹汤加减方降低佐剂性关节炎大鼠外周血T细胞cAMP水平和CD4+/CD8+T细胞比值[J].细胞与分子免疫学杂志,2018,34(2):110-114.
[13]袁秀泽,邹盛勤,王晓刚,等.白芍总苷在佐剂性关节炎大鼠与正常大鼠体内的药动学差异[J].中国实验方剂学杂志,2016,22(20):86-89.
[14]马钰泱,狄泽敏,曹晴,等.佐剂性关节炎大鼠滑膜及血清中MANF的表达及其与炎症的相关性[J].中国药理学通报,2018,34(4):537-543.
[15]姜辉,秦秀娟,万磊,等.五味温通除痹胶囊对佐剂性关节炎大鼠自噬蛋白Beclin-1、LC3-Ⅱ表达的影响[J].中成药,2017,39(8):1566-1572.
[16]刘肃,张鑫,王春生.类风湿性关节患者血清炎性细胞因子水平及其临床意义分析[J].基因组学与应用生物学,2018,37(9):4100-4105.
[17]Roeleveld DM,Marijnissen RJ,Walgreen B,et al. Higher efficacy of anti-IL-6/IL-21 combination therapy compared to monotherapy in the induction phase of Th17-driven experimental arthritis[J]. PLoS One,2017,12(2):e0171757.
[18]GongdaoJIANG,BijiangWAN,WeiHUANG,etal.Influence of acupotomy loosing on IL-6,IL-10 and TNF-αin synovial fluid of rheumatoid arthritis patients with elbow joint stiffness[J]. World Journal of Acupuncture-Moxibustion,2018,28(2):21-26.
[19]Jae-Myung Yoo,Ju-Hye Yang,Young Soo Kim,et al. Inhibitory Effect of Loranthus parasiticus on IgE-Mediated Allergic Responses in RBL-2H3 Cells[J]. Mediators ofInflammation,2016,2016:75-77.
[20]PengFe Han,Lei Wei,Zhi-Qing Duan,et al. Contribution of IL-1β,6 and TNF-αto the form of post-traumatic osteoarthritis induced by“idealized”anterior cruciate ligament reconstruction in a porcine model[J]. International Immunopharmacology,2018,65:212-220.
[21]Jialei Jin,Xingfang Yu,Zhichao Hu,et al. Isofraxidin targets the TLR4/MD-2 axis to prevent osteoarthritis development[J].Food&function,2018,9(11):5641-5652.
[22]Mateen S,Zafar A,Moin S,et al. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis[J]. Clin Chim Acta,2016,13(455):161-171.
[23]Rao DA,Gurish MF,Marshall JL,et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis[J]. Nature,2017,542(7639):110-114.
[24]MoyaP,SalazarJ,ArranzMJ,etal.Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients[J]. Pharmacogenomics,2015,17(1):25-29.
[25]Brown PM,Pratt AG,Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis,and the search for biomarkers[J]. Nat Rev Rheumatol,2016,12(12):731-742.
[26]Xie Z,Liu G,Tang P,et al. Bone-targeted methotrexatealendronate conjugate inhibits osteoclastogenesis in vitro and prevents bone loss and inflammation of collagen-induced arthritis in vivo[J]. Drug Delivery,2018,25(1):187-197.
[27]Lamb YN,Deeks ED. Sarilumab:A Review in Moderate to Severe Rheumatoid Arthritis[J]. Drugs,2018,78(9):929-940.
[28]Takahashi N,Kojima T,Kida D,et al. Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid arthritis patients:Results from a multicenter registry system[J]. Modern Rheumatology,2018,15(9):1-23.
[29]许霞,杜欢,程卉,等.程氏蠲痹汤加减对佐剂关节炎大鼠药效影响[J].辽宁中医药大学学报,2016,18(10):17-20.
[30]Xiang N,Li XM,Zhang MJ,et al. Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis[J]. Int Immunopharmacol,2015,28(1):802-807.
[31]Yang S,Xing Z,Liu T,et al. Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis[J]. Drug Design Development and Therapy,2018,12:463-473.
[32]Qian C,Kuang M,Wang Y. Effect of Qianghuo Erhuang Decoction on T Regulatory and T Helper 17 Cells in Treatment of Adjuvant-induced Arthritis in Rats[J]. Scientific Reports,2017,7(1):17198.1
[2]Chemin K,Klareskog L,Malmstrom V. Is rheumatoid arthritis an autoimmune disease[J]. Curr Opin Rheumatol,2016,28(2):181-188.
[3]Terao C,Ikari K,Nakayamada S,et al. A twin study of rheumatoid arthritis in the Japanese population[J]. Mod Rheumatol,2016,26(5):685-689.
[4]Neumann E,Frommer K,Diller M,et al. Rheumatoid arthritis[J].Zeitschrift fur Rheumatologie,2018,77(9):769-775.
[5]Zhang A,Lee YC. Mechanisms for Joint Pain in Rheumatoid Arthritis(RA):from Cytokines to Central Sensitization[J].Current Osteoporosis Reports,2018,16(5):603-610.
[6]王冰,高明利.四神煎治疗气阴两虚型类风湿关节炎的研究进展[J].风湿病与关节炎,2018,7(6):76-80.
[7]Tank ND,Karelia BN,Vegada BN. Biological Response Modifiers in Rheumatoid Arthritis:Systematic Review and Meta-analysis of Safety[J]. J Pharmacol Pharmacother,2017,8(3):92-105.
[8]Ishiguro N,Dougados M,Cai Z,et al. Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis:Post hocanalyses of overall and Japanese results from two phase 3 clinical trials[J]. Mod Rheumatol,2018,28(6):1-10.
[9]姜泉,王海隆,巩勋,等.类风湿关节炎病证结合诊疗指南[J].中医杂志,2018,59(20):1794-1800.
[10]许霞,杜欢,程卉,等.程氏蠲痹汤加减方含药血清对佐剂性关节炎大鼠外周血单核细胞TNF-α和IL-1β表达的影响[J].安徽中医药大学学报,2016,35(6):83-86.
[11]许霞,程卉,曹健,等.程氏蠲痹汤加减方降低佐剂关节炎大鼠滑膜组织前列腺素E受体4(PTGER4)的水平[J].细胞与分子免疫学杂志,2017,33(6):736-740.
[12]许霞,杜欢,吴亚兰,等.程氏蠲痹汤加减方降低佐剂性关节炎大鼠外周血T细胞cAMP水平和CD4+/CD8+T细胞比值[J].细胞与分子免疫学杂志,2018,34(2):110-114.
[13]袁秀泽,邹盛勤,王晓刚,等.白芍总苷在佐剂性关节炎大鼠与正常大鼠体内的药动学差异[J].中国实验方剂学杂志,2016,22(20):86-89.
[14]马钰泱,狄泽敏,曹晴,等.佐剂性关节炎大鼠滑膜及血清中MANF的表达及其与炎症的相关性[J].中国药理学通报,2018,34(4):537-543.
[15]姜辉,秦秀娟,万磊,等.五味温通除痹胶囊对佐剂性关节炎大鼠自噬蛋白Beclin-1、LC3-Ⅱ表达的影响[J].中成药,2017,39(8):1566-1572.
[16]刘肃,张鑫,王春生.类风湿性关节患者血清炎性细胞因子水平及其临床意义分析[J].基因组学与应用生物学,2018,37(9):4100-4105.
[17]Roeleveld DM,Marijnissen RJ,Walgreen B,et al. Higher efficacy of anti-IL-6/IL-21 combination therapy compared to monotherapy in the induction phase of Th17-driven experimental arthritis[J]. PLoS One,2017,12(2):e0171757.
[18]GongdaoJIANG,BijiangWAN,WeiHUANG,etal.Influence of acupotomy loosing on IL-6,IL-10 and TNF-αin synovial fluid of rheumatoid arthritis patients with elbow joint stiffness[J]. World Journal of Acupuncture-Moxibustion,2018,28(2):21-26.
[19]Jae-Myung Yoo,Ju-Hye Yang,Young Soo Kim,et al. Inhibitory Effect of Loranthus parasiticus on IgE-Mediated Allergic Responses in RBL-2H3 Cells[J]. Mediators ofInflammation,2016,2016:75-77.
[20]PengFe Han,Lei Wei,Zhi-Qing Duan,et al. Contribution of IL-1β,6 and TNF-αto the form of post-traumatic osteoarthritis induced by“idealized”anterior cruciate ligament reconstruction in a porcine model[J]. International Immunopharmacology,2018,65:212-220.
[21]Jialei Jin,Xingfang Yu,Zhichao Hu,et al. Isofraxidin targets the TLR4/MD-2 axis to prevent osteoarthritis development[J].Food&function,2018,9(11):5641-5652.
[22]Mateen S,Zafar A,Moin S,et al. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis[J]. Clin Chim Acta,2016,13(455):161-171.
[23]Rao DA,Gurish MF,Marshall JL,et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis[J]. Nature,2017,542(7639):110-114.
[24]MoyaP,SalazarJ,ArranzMJ,etal.Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients[J]. Pharmacogenomics,2015,17(1):25-29.
[25]Brown PM,Pratt AG,Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis,and the search for biomarkers[J]. Nat Rev Rheumatol,2016,12(12):731-742.
[26]Xie Z,Liu G,Tang P,et al. Bone-targeted methotrexatealendronate conjugate inhibits osteoclastogenesis in vitro and prevents bone loss and inflammation of collagen-induced arthritis in vivo[J]. Drug Delivery,2018,25(1):187-197.
[27]Lamb YN,Deeks ED. Sarilumab:A Review in Moderate to Severe Rheumatoid Arthritis[J]. Drugs,2018,78(9):929-940.
[28]Takahashi N,Kojima T,Kida D,et al. Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid arthritis patients:Results from a multicenter registry system[J]. Modern Rheumatology,2018,15(9):1-23.
[29]许霞,杜欢,程卉,等.程氏蠲痹汤加减对佐剂关节炎大鼠药效影响[J].辽宁中医药大学学报,2016,18(10):17-20.
[30]Xiang N,Li XM,Zhang MJ,et al. Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis[J]. Int Immunopharmacol,2015,28(1):802-807.
[31]Yang S,Xing Z,Liu T,et al. Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis[J]. Drug Design Development and Therapy,2018,12:463-473.
[32]Qian C,Kuang M,Wang Y. Effect of Qianghuo Erhuang Decoction on T Regulatory and T Helper 17 Cells in Treatment of Adjuvant-induced Arthritis in Rats[J]. Scientific Reports,2017,7(1):17198.1