祖师麻片对牛Ⅱ型胶原诱导大鼠关节炎的药效学研究
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摘要
目的探究祖师麻片对牛Ⅱ型胶原诱发大鼠关节炎的药效学作用。方法采用牛Ⅱ型胶原诱导的关节炎(collagen-induced anhritis,CIA)动物模型,来观察祖师麻片对CIA模型大鼠的关节炎指数(arthritis index,AI),血清中环氧化酶-2(cyclooxygenase-2,COX-2)、结缔组织生长因子(connective tissue growth factor,CTGF)、风湿因子(rheumatoid factor,RF)、免疫球蛋白G(immunoglobulin G,Ig G)、白介素-6(interleukin-6,IL-6)、前列腺素-2(prostaglandin E-2,PGE-2)、肿瘤坏死因子-α(tumor necrosis factor-a,TNF-α)的含量,膝关节番红O-固绿染色,镜下观察关节软骨的一般形态,并对膝关节软骨进行Mankin’ s评分。结果与模型组比较,祖师麻片剂量组大鼠AI评分显著降低(P <0.01);血清中CTGF、Ig G、RF、COX-2、IL-6、PGE-2、TNF-α含量显著降低(P <0.05或P <0.01);软骨细胞数量稍有减少,染色丢失较少,潮线基本完整,Mankin’ s评分评分显著降低(P <0.01)。结论祖师麻片对Ⅱ型胶原诱导的类风湿关节炎有显著改善作用,其机制可能与抗炎、免疫调节作用有关。
Objective To explore the pharmacodynamic effect of Zushima Tablet on bovine type II collagen induced arthritis in rats. Methods An animal model of CIA was used to observe the AI and the serum, COX-2 CTGF, RF, IgG, IL-6, PGE-2 and TNF-α. Knee red O-solid green staining of the knee joint, the general morphology of articular cartilage was observed under the microscope, and the Mankin's score was evaluated for the knee joint cartilage. Results Compared with the model group, the AI scores of the ancestral numb tablet group were significantly lower(P < 0.01). The levels of CTGF, IgG, RF, COX-2, IL-6, PGE-2 and TNF-α in serum were significantly lower(P < 0.05 or P < 0.01). The number of chondrocytes was slightly reduced. The stain loss was less and the tidal line was almost complete. The Mankin's score was significantly lower(P < 0.01). Conclusion Zushima Tablet can significantly improve type II collagen-induced rheumatoid arthritis, which mechanism may be related to anti-inflammatory and immunoregulatory effects.
Objective To explore the pharmacodynamic effect of Zushima Tablet on bovine type II collagen induced arthritis in rats. Methods An animal model of CIA was used to observe the AI and the serum, COX-2 CTGF, RF, IgG, IL-6, PGE-2 and TNF-α. Knee red O-solid green staining of the knee joint, the general morphology of articular cartilage was observed under the microscope, and the Mankin's score was evaluated for the knee joint cartilage. Results Compared with the model group, the AI scores of the ancestral numb tablet group were significantly lower(P < 0.01). The levels of CTGF, IgG, RF, COX-2, IL-6, PGE-2 and TNF-α in serum were significantly lower(P < 0.05 or P < 0.01). The number of chondrocytes was slightly reduced. The stain loss was less and the tidal line was almost complete. The Mankin's score was significantly lower(P < 0.01). Conclusion Zushima Tablet can significantly improve type II collagen-induced rheumatoid arthritis, which mechanism may be related to anti-inflammatory and immunoregulatory effects.
引文
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[13]CHEN H,WANG J,WANG J,et al.Serum connective tissue growth factor is a highly discriminatory biomarker for the diagnosis of rheumatoid arthritis[J].Arthritis Res Ther,2017,19(1):257-265.
[14]BERNTSON L,NORDAL E,FASTH A,et al.Anti-type II collagen antibodies,anti-CCP,IgA RF and IgM RF are associated with joint damage,assessed eight years after onset of juvenile idiopathic arthritis(JIA)[J].Pediatric Rheumatology,2014,12(1):1-7.
[15]LIM M A,LOUIE B,FORD D,et al.Development of the digital arthritis Index,a novel metric to measure disease parameters in a rat model of rheumatoid arthritis[J].Front Pharmacol,2017(8):818-836.
[16]LAKSHMAN T R,DEB J,PAINE T K.Anti-inflammatory activity and enhanced COX-2 selectivity of nitric oxidedonating zinc(ii)-NSAID complexes[J].Dalton Trans,2016,45(36):14053-14057.
[17]NARAZAKI M,TANAKA T,KISHIMOTO T.The role and therapeutic targeting of IL-6 in rheumatoid arthritis[J].Expert Rev Clin Immunol,2017,13(6):535-551.
[18]YOSHIMATSU H,OKAZAKI F,IEIRI I,et al.Mechanism of the 24-hour rhythm of tumor necrosis factor-alpha formed by onset of rheumatoid arthritis[J].Chronobiol Int,2014,31(4):564-571.
[2]ANGELOTTI F,PARMA A,CAFARO G,et al.One year in review 2017:pathogenesis of rheumatoid arthritis[J].Clin Exp Rheumatol,2017,35(3):368-378.
[3]WOOD P R,CAPLAN L.Drug-induced gastrointestinal and hepatic disease associated with biologics and nonbiologic disease-modifying antirheumatic drugs[J].Rheum Dis Clin North Am,2018,44(1):29-43.
[4]MCGETTIGAN P,HENRY D.Cardiovascular risk with non-steroidal anti-inflammatory drugs:systematic review of population-based controlled observational studies[J].PLoSMed,2011,8(9):e1001098.
[5]王宇华,许惠琴,狄留庆,等.祖师麻提取物的镇痛与抗炎作用研究[J].中草药,2007,38(11):1697-1700.
[6]卓诗勤,葛卫红,史丽云.祖师麻甲素对巨噬细胞抗金黄色葡萄球菌的作用研究[J].云南中医学院学报,2016,39(5):1-6.
[7]YANG X,HUANG M,ZHENG S,et al.Liquid chromatography with mass spectrometry and NMR spectroscopy based discovery of cytotoxic principles from daphne tangutica maxim[J].J Sep Sci,2016,39(11):2179-2187.
[8]国家药典委员会.中华人民共和国药典[M].北京:中国医药科技出版社,2015:1321.
[9]SONG H P,LI X,YU R,et al.Phenotypic characterization of type II collagen-induced arthritis in Wistar rats[J].Exp Ther Med,2015,10(4):1483-1488.
[10]MATHEW L E,RAJAGOPAL V,A H.Betulinic acid and fluvastatin exhibits synergistic effect on toll-like receptor-4mediated anti-atherogenic mechanism in type II collagen induced arthritis[J].Biom pharmacother,2017,93:681-694.
[11]唐涛,邢崇慧,孙先润,等.过度运动对大鼠膝关节损伤的机理探究[J].中国矫形外科杂志,2016,24(14):1314-1320.
[12]MIHARA T,TANISHIMA S,TANIDA A,et al.Histological evaluation of lumbar spine changes in rats with collageninduced arthritis[J].Yonago Acta Med,2018,61(1):66-71.
[13]CHEN H,WANG J,WANG J,et al.Serum connective tissue growth factor is a highly discriminatory biomarker for the diagnosis of rheumatoid arthritis[J].Arthritis Res Ther,2017,19(1):257-265.
[14]BERNTSON L,NORDAL E,FASTH A,et al.Anti-type II collagen antibodies,anti-CCP,IgA RF and IgM RF are associated with joint damage,assessed eight years after onset of juvenile idiopathic arthritis(JIA)[J].Pediatric Rheumatology,2014,12(1):1-7.
[15]LIM M A,LOUIE B,FORD D,et al.Development of the digital arthritis Index,a novel metric to measure disease parameters in a rat model of rheumatoid arthritis[J].Front Pharmacol,2017(8):818-836.
[16]LAKSHMAN T R,DEB J,PAINE T K.Anti-inflammatory activity and enhanced COX-2 selectivity of nitric oxidedonating zinc(ii)-NSAID complexes[J].Dalton Trans,2016,45(36):14053-14057.
[17]NARAZAKI M,TANAKA T,KISHIMOTO T.The role and therapeutic targeting of IL-6 in rheumatoid arthritis[J].Expert Rev Clin Immunol,2017,13(6):535-551.
[18]YOSHIMATSU H,OKAZAKI F,IEIRI I,et al.Mechanism of the 24-hour rhythm of tumor necrosis factor-alpha formed by onset of rheumatoid arthritis[J].Chronobiol Int,2014,31(4):564-571.