风湿宁胶囊对类风湿关节炎风寒湿痹动物模型的关节保护及抗炎作用
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摘要
目的:从抗炎及关节保护方面探讨风湿宁(FSN)胶囊治疗类风湿性关节炎(RA)的药物作用机制。方法:将120只雄性新西兰白兔随机分为正常组、模型组、甲氨蝶呤组、风湿宁低、中、高剂量组,每组20只。除正常组外,其余各组建立胶原诱导性关节炎(CIA)加风寒湿刺激的风寒湿痹动物模型,造模成功以后,风湿宁低、中、高剂量组分别按剂量0.33,0.66,1.32 g·kg~(-1)给予风湿宁胶囊水溶液,甲氨蝶呤组给予1.0 mg·kg~(-1)的甲氨蝶呤片水溶液,正常组灌胃生理盐水,各组按剂量4 m L·kg~(-1)灌胃,每日1次,连续7 d。观察风湿宁胶囊对RA白兔风寒湿痹模型的一般情况、关节肿胀程度,实时荧光定量聚合酶链反应(Real-time PCR)检测各组关节滑膜组织炎症因子白细胞介素(IL)~(-1)β,IL-6,肿瘤坏死因子(TNF)-α信使核糖核酸(mRNA)的表达量及核转录因子-κB(NF-κB)受体激活剂配体(RANKL)mRNA的表达量。结果:风湿宁胶囊可明显改善RA兔生存状态,减轻RA兔后肢膝关节的肿胀,降低膝关节表面温度和关节炎积分,能够显著降低RA兔滑膜组织IL~(-1)β,IL-6,TNF-α,RANKL mRNA的表达。结论:风湿宁胶囊具有抑制关节滑膜组织中炎症因子和RANKL的表达的作用,可有效减轻RA的炎症反应和骨质破坏,从而对RA取得疗效。
Objective: To discuss the anti-inflammatory and joint protection effect of Fengshining( FSN)capsule in treatment of rheumatoid arthritis( RA) and its action mechanism. Method: The 120 male New Zealand white rabbits were randomly divided into normal control group,model group,Methotrexate group,low-dose,middle-dose and high-dose FSN groups,with 20 in each group. The collagen-induced arthritis( CIA) and wind-cold dampness rheumatoid arthritis model were established in the groups,except for the normal control group. Low-dose,middle-dose and high-dose FSN groups were given aqueous solution of 0. 33,0. 66,1. 32 g·kg~(-1) FSN capsule respectively,the methotrexate group was given aqueous solution of 1. 0 mg·kg~(-1) methotrexate tablets,while the normal control group and the model group were given saline solution. Each group was intragastrically administrated with 4 m L·kg~(-1) of corresponding medicines,once a day for 7 days. The effect of FSN capsule on general conditions,joint swelling degree of the animal model were observed,and the expressions of inflammatory factor interleukin( IL)~(-1)β,IL-6,tumor necrosis factor( TNF)-α messenger RNA( mRNA) and receptor activator of nuclear factor kappa B ligand( RANKL) mRNA in RA synovium tissues were detected with Real-time PCR method. Result: FSN capsule could improve the living state of RA rabbits significantly,reduce the swelling and arthritis score of stifle,and obviously decrease the expressions of IL~(-1)β,IL-6,TNF-α and RANKL mRNA in RA synovial tissues. Conclusion: FSN capsule has the effect in inhibiting the expression of inflammation factor and RANKL in synovial tissues,and could effectively alleviate inflammation and bone damage,so as to show a curative effect on RA.
Objective: To discuss the anti-inflammatory and joint protection effect of Fengshining( FSN)capsule in treatment of rheumatoid arthritis( RA) and its action mechanism. Method: The 120 male New Zealand white rabbits were randomly divided into normal control group,model group,Methotrexate group,low-dose,middle-dose and high-dose FSN groups,with 20 in each group. The collagen-induced arthritis( CIA) and wind-cold dampness rheumatoid arthritis model were established in the groups,except for the normal control group. Low-dose,middle-dose and high-dose FSN groups were given aqueous solution of 0. 33,0. 66,1. 32 g·kg~(-1) FSN capsule respectively,the methotrexate group was given aqueous solution of 1. 0 mg·kg~(-1) methotrexate tablets,while the normal control group and the model group were given saline solution. Each group was intragastrically administrated with 4 m L·kg~(-1) of corresponding medicines,once a day for 7 days. The effect of FSN capsule on general conditions,joint swelling degree of the animal model were observed,and the expressions of inflammatory factor interleukin( IL)~(-1)β,IL-6,tumor necrosis factor( TNF)-α messenger RNA( mRNA) and receptor activator of nuclear factor kappa B ligand( RANKL) mRNA in RA synovium tissues were detected with Real-time PCR method. Result: FSN capsule could improve the living state of RA rabbits significantly,reduce the swelling and arthritis score of stifle,and obviously decrease the expressions of IL~(-1)β,IL-6,TNF-α and RANKL mRNA in RA synovial tissues. Conclusion: FSN capsule has the effect in inhibiting the expression of inflammation factor and RANKL in synovial tissues,and could effectively alleviate inflammation and bone damage,so as to show a curative effect on RA.
引文
[1]魏雪敏,梅轶芳,张志毅.白细胞介素-17在类风湿关节炎发病机制和治疗中的研究进展[J].中华内科杂志,2012,51(6):492-494.
[2]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.
[3]WEI S,Kitaura H,ZHOU P,et al.IL-1 mediates TNFinduced osteoclastogenesis[J].J Clin Invest,2005,115(2):282-290.
[4]赵建平,刘光珍,王裕颐.风湿宁胶囊治疗类风湿性关节炎疗效观察[J].山西中医,1999,15(6):8-10.
[5]马艳苗,王永辉,李艳彦,等.风湿宁胶囊对胶原诱导性关节炎大鼠滑膜细胞超微结构及细胞凋亡相关基因表达的影响[J].中医杂志,2013,54(4):326-335.
[6]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型的研究[J].中医杂志,1996,37(8):492-496.
[7]尹俊滨,高飞,张瀚文,等.治疗类风湿关节炎的研究进展[J].现代生物医学进展,2009,9(21):4172-4174.
[8]林文棠,朱平.临床免疫学[M].西安:第四军医大学出版社,2002:25-26.
[9]Dayer J M.Evidence for the biological modulation of IL-1 activity:the role of IL-1Ra[J].Clin Exp Rheumatol,2004,20(5 Suppl 27):S20-S24.
[10]Naka T,Nishimoto N,Kishimoto T.The paradigm of IL-6:from basic science to medicine[J].Arthritis Res,2002,4(3):233-242.
[11]Miranda-Carús M E,Balsa A,Benito-Miguel M,et al.IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis:effect of methotrexate[J].J Immunol,2004,173(2):1463-1476.
[12]Yousef A,Sabiha A,Teruhisa H.TNF receptor type 1regulates RANK ligand expression by stromal cells and modu Lates osteoclastogenesis[J].J Cell Biochem,2004,93(5):980-989.
[13]周学平,周玲玲,陈晨,等.清络通痹颗粒干预类风湿关节炎破骨细胞分化相关因子分泌的研究[J].中国免疫学杂志,2014,30(2):202-208.
[14]Page G,Miossec P.RANK and ANKL expression as markers of dendritic cell-T cell interactions in paired samples of rheumatoid synovium and lymph nodes[J].Arthritis Rheum,2005,52(8):2307-2312.
[15]冯振宇,马小娟,孟霜,等.风湿宁胶囊对RA兔滑膜组织病理学的影响[J].中药材,2016,12(39):2867-2869.
[2]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.
[3]WEI S,Kitaura H,ZHOU P,et al.IL-1 mediates TNFinduced osteoclastogenesis[J].J Clin Invest,2005,115(2):282-290.
[4]赵建平,刘光珍,王裕颐.风湿宁胶囊治疗类风湿性关节炎疗效观察[J].山西中医,1999,15(6):8-10.
[5]马艳苗,王永辉,李艳彦,等.风湿宁胶囊对胶原诱导性关节炎大鼠滑膜细胞超微结构及细胞凋亡相关基因表达的影响[J].中医杂志,2013,54(4):326-335.
[6]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型的研究[J].中医杂志,1996,37(8):492-496.
[7]尹俊滨,高飞,张瀚文,等.治疗类风湿关节炎的研究进展[J].现代生物医学进展,2009,9(21):4172-4174.
[8]林文棠,朱平.临床免疫学[M].西安:第四军医大学出版社,2002:25-26.
[9]Dayer J M.Evidence for the biological modulation of IL-1 activity:the role of IL-1Ra[J].Clin Exp Rheumatol,2004,20(5 Suppl 27):S20-S24.
[10]Naka T,Nishimoto N,Kishimoto T.The paradigm of IL-6:from basic science to medicine[J].Arthritis Res,2002,4(3):233-242.
[11]Miranda-Carús M E,Balsa A,Benito-Miguel M,et al.IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis:effect of methotrexate[J].J Immunol,2004,173(2):1463-1476.
[12]Yousef A,Sabiha A,Teruhisa H.TNF receptor type 1regulates RANK ligand expression by stromal cells and modu Lates osteoclastogenesis[J].J Cell Biochem,2004,93(5):980-989.
[13]周学平,周玲玲,陈晨,等.清络通痹颗粒干预类风湿关节炎破骨细胞分化相关因子分泌的研究[J].中国免疫学杂志,2014,30(2):202-208.
[14]Page G,Miossec P.RANK and ANKL expression as markers of dendritic cell-T cell interactions in paired samples of rheumatoid synovium and lymph nodes[J].Arthritis Rheum,2005,52(8):2307-2312.
[15]冯振宇,马小娟,孟霜,等.风湿宁胶囊对RA兔滑膜组织病理学的影响[J].中药材,2016,12(39):2867-2869.