复方芪芎颗粒对佐剂性关节炎大鼠的抗炎消肿作用及TIR域信号通路影响
|
摘要
目的:探究复方芪芎颗粒对佐剂性关节炎(adjuvant arthritis,AA)大鼠滑膜组织的抗炎消肿作用及对TLR4、MyD88及SIGIRR之间信号传导机制的影响。方法:将实验大鼠随机分组并造模,共分为6组,除正常组外,其余5组大鼠予弗氏完全佐剂注射进行造模并给予雷公藤苷或不同剂量浓度复方芪芎颗粒药物灌胃,对比造模前、给药前、干预4周后各组大鼠一般情况变化及致炎侧的足趾周径变化,评估大鼠各关节的炎症指数(arthritis index,AI),检测各组大鼠滑膜组织中TLR4、MyD88及SIGIRR蛋白的表达程度。结果:给药后4周,雷公藤组大鼠足趾周径低于模型组、正常组,差异有统计学意义(P<0.01或P<0.05)。给药后复方芪芎颗粒组大鼠足趾周径下降,高剂量组显著下降。给药4周后,复方芪芎颗粒低、中、高剂量组、雷公藤组大鼠AI均低于模型组(P<0.01);复方芪芎颗粒高、中剂量组大鼠AI均低于复方芪芎颗粒低剂量组与雷公藤组(P<0.05)。复方芪芎颗粒中、高剂量组、雷公藤组大鼠TLR4、MyD88蛋白表达均低于模型组(P<0.01),SIGIRR蛋白表达高于模型组(P<0.01)。复方芪芎颗粒高剂量组大鼠TLR4、MyD88蛋白表达低于雷公藤组(P<0.05),SIGIRR蛋白表达高于雷公藤组(P<0.05)。结论:复方芪芎颗粒对佐剂性关节炎大鼠有抗炎消肿作用,其作用机制与抑制异常激活TLR4、MyD88的表达及上调SIGIRR蛋白的表达相关。
Objective: To investigate the anti-inflammatory and detumescence of compound Qixiong particles on the synovial tissue of adjuvant arthritis(AA) rats and the signal transduction mechanism between TLR4,MyD88 and SIGIRR. Method: The experimental rats were randomly divided into six groups. Except the normal group, the other five groups were injected with Freund's complete adjuvant and given Tripterygium wilfordii glycoside or compound Qixiong granules of different doses by gastric perfusion. The changes of general condition and toe circumference of inflammation side were compared, before and after four weeks of intervention, and the arthritis of rats was evaluated. The expression of TLR4, MyD88 and SIGIRR protein in synovial tissue of rats in each group was detected by arthritis index(AI). Results: Four weeks after administration, the toe circumference of rats in Tripterygium wilfordii group was lower than that of model group and normal group(P<0.01 or P<0.05).After administration, the toe circumference of rats in the compound Qixiong granule group decreased, while that in the high dose group decreased significantly. Four weeks after administration, AI of rats in low, medium, high dose group and Tripterygium wilfordii group was lower than that of model group(P<0.01), and AI of rats in high and medium dose group of compound Qixiong granule was lower than that of low dose group and Tripterygium wilfordii group(P<0.05). The expression of TLR4 and MyD88 protein in the middle, high dose and Tripterygium wilfordii groups were lower than that in the model group(P<0.01), and the expression of SIGIRR protein in the model group was higher than that in the model group(P<0.01). The expression of TLR4 and MyD88 protein in high dose group was lower than that in Tripterygium wilfordii group(P <0.05), and the expression of SIGIRR protein was higher than that in Tripterygium wilfordii group(P<0.05). Conclusion: Compound Qixiong particles has anti-inflammatory and anti-swelling effects on adjuvant arthritis rats. Its mechanism is related to inhibiting abnormal activation of TLR4 and MyD88 expression and up-regulating SIGIRR protein expression.
Objective: To investigate the anti-inflammatory and detumescence of compound Qixiong particles on the synovial tissue of adjuvant arthritis(AA) rats and the signal transduction mechanism between TLR4,MyD88 and SIGIRR. Method: The experimental rats were randomly divided into six groups. Except the normal group, the other five groups were injected with Freund's complete adjuvant and given Tripterygium wilfordii glycoside or compound Qixiong granules of different doses by gastric perfusion. The changes of general condition and toe circumference of inflammation side were compared, before and after four weeks of intervention, and the arthritis of rats was evaluated. The expression of TLR4, MyD88 and SIGIRR protein in synovial tissue of rats in each group was detected by arthritis index(AI). Results: Four weeks after administration, the toe circumference of rats in Tripterygium wilfordii group was lower than that of model group and normal group(P<0.01 or P<0.05).After administration, the toe circumference of rats in the compound Qixiong granule group decreased, while that in the high dose group decreased significantly. Four weeks after administration, AI of rats in low, medium, high dose group and Tripterygium wilfordii group was lower than that of model group(P<0.01), and AI of rats in high and medium dose group of compound Qixiong granule was lower than that of low dose group and Tripterygium wilfordii group(P<0.05). The expression of TLR4 and MyD88 protein in the middle, high dose and Tripterygium wilfordii groups were lower than that in the model group(P<0.01), and the expression of SIGIRR protein in the model group was higher than that in the model group(P<0.01). The expression of TLR4 and MyD88 protein in high dose group was lower than that in Tripterygium wilfordii group(P <0.05), and the expression of SIGIRR protein was higher than that in Tripterygium wilfordii group(P<0.05). Conclusion: Compound Qixiong particles has anti-inflammatory and anti-swelling effects on adjuvant arthritis rats. Its mechanism is related to inhibiting abnormal activation of TLR4 and MyD88 expression and up-regulating SIGIRR protein expression.
引文
[1] LAU C S, CHIA F, HARRISON A, et al. APLAR rheumatoid arthritis treatment recommendations[J]. Int J Rheum Dis,2015,18(7):685-713.
[2] XU M, GUO Q, WANG S, et al. Anti-rheumatoid arthritic effects of Saussurea involucrata on type II collagen-induced arthritis in rats[J]. Food&Function,2016,7(2):763-770.
[3]中华医学会风湿病学分会.类风湿关节炎诊断及治疗指南[J].中华风湿病学杂志,2010,14(4):265-270.
[4]郭锦晨,刘健,汪元,等.中医药内外合治类风湿关节炎的研究进展[J].中国临床保健杂志,2016,19(3):329-333.
[5]王俊伟,陈利锋,王华松,等.复方芪芎颗粒治疗类风湿性关节炎的实验研究[J].华南国防医学杂志,2016,30(3):145-148.
[6]陈利锋,王军,林慧,等.复方芪芎颗粒对佐剂性关节炎大鼠抗炎作用的实验研究[J].华南国防医学杂志,2015,29(6):415-418.
[7]陈利锋,张蓉,王俊伟,等.益气活血方对兔佐剂性关节炎关节软骨的影响及机制研究[J].华南国防医学杂志,2016,30(10):623-626.
[8]陈利锋,丰瑞兵,王华松,等.益气活血方对关节炎大鼠滑膜组织IL-8、NF-κB的影响[J].湖北中医药大学学报,2017,19(2):4-8.
[9]丰瑞兵,陈利锋,王华松,等.益气活血方对佐剂型关节炎大鼠滑膜组织TLR2、TLR9的影响[J].中医药导报,2017,23(17):25-27.
[10]高宜军,董启榕.兔类风湿性关节炎模型的诱导机制及组织病理学的研究[J].苏州大学学报(医学版),2005,25(5):63-66.
[11]龚爱迪,欧阳亚琳,张学英,等.国内外类风湿性关节炎动物实验模型研究进展分析[J].世界最新医学信息文摘,2015,15(19):25-27.
[12]刘永平,陈建双,赵波,等.赤雹根总皂苷对实验性佐剂型关节炎镇痛作用的研究[J].辽宁中医杂志,2011,38(8):1659-1661.
[13]晋小荣,朱苗苗,高永翔,等.TOLL样受体介导信号通路与类风湿关节炎关系的研究进展[J].湖南中医杂志,2017,33(10):193-195.
[14]陈利锋,刘辉,王华松,等.复方芪芎颗粒治疗类风湿性关节炎的机制[J].中国医院药学杂志,2017,37(20):2024-2028.
[15] GONG J, WEI T, STARK R W, et al. Inhibition of Toll-like receptors TLR4 and 7 signaling pathways by SIGIRR:A computational approach[J]. Journal of Structural Biology,2010,169(3):323-330.
[16] PARK S Y,LEE S W,BAEK S H,et al. Suppression of PU.1-linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis[J]. British Journal of Pharmacology,2013,168(6):1401-1411.
[17] CEREZO L A, REMAKOVA M, TOM IK M, et al.The metastasis-associated protein S100A4 promotes the inflammatory response of mononuclear cells via the TLR4 signalling pathway in rheumatoid arthritis[J].Rheumatology,2014,53(8):1520-1526.
[18] YAMAGUCHI R,SAKAMOTO A,YAMAMOTO T,et al. Differential regulation of IL-23 production in M1macrophages by TIR8/SIGIRR through TLR4-or TLR7/8-mediated signaling[J]. Cytokine,2017,99(11):310-315.
[19] KIM S, BANG J, SON C, et al. Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway[J].The Korean Journal of Internal Medicine,2016,33(3):612-621.
[20] RIVA F,BONAVITA E,BARBATI E,et al. TIR8/SIGIRR is an Interleukin-1 Receptor/Toll Like Receptor Family Member with Regulatory Functions in Inflammation and Immunity[J]. Front Immunol,2012,3(10):322-335.
[21] YAMAGUCHI R,SAKAMOTO A,YAMAGUCHI R,et al.Transcription factor specificity protein 1 modulates TGFbeta1/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P[J]. Cytokine,2018,108(8):24-36.
[22] BAUMAN T M, BECKA A J, SEHGAL P D, et al.SIGIRR/TIR8,an important regulator of TLR4 and IL-1R-mediated NF-kappaB activation,predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas[J]. Hum Pathol,2015,46(11):1744-1751.
[2] XU M, GUO Q, WANG S, et al. Anti-rheumatoid arthritic effects of Saussurea involucrata on type II collagen-induced arthritis in rats[J]. Food&Function,2016,7(2):763-770.
[3]中华医学会风湿病学分会.类风湿关节炎诊断及治疗指南[J].中华风湿病学杂志,2010,14(4):265-270.
[4]郭锦晨,刘健,汪元,等.中医药内外合治类风湿关节炎的研究进展[J].中国临床保健杂志,2016,19(3):329-333.
[5]王俊伟,陈利锋,王华松,等.复方芪芎颗粒治疗类风湿性关节炎的实验研究[J].华南国防医学杂志,2016,30(3):145-148.
[6]陈利锋,王军,林慧,等.复方芪芎颗粒对佐剂性关节炎大鼠抗炎作用的实验研究[J].华南国防医学杂志,2015,29(6):415-418.
[7]陈利锋,张蓉,王俊伟,等.益气活血方对兔佐剂性关节炎关节软骨的影响及机制研究[J].华南国防医学杂志,2016,30(10):623-626.
[8]陈利锋,丰瑞兵,王华松,等.益气活血方对关节炎大鼠滑膜组织IL-8、NF-κB的影响[J].湖北中医药大学学报,2017,19(2):4-8.
[9]丰瑞兵,陈利锋,王华松,等.益气活血方对佐剂型关节炎大鼠滑膜组织TLR2、TLR9的影响[J].中医药导报,2017,23(17):25-27.
[10]高宜军,董启榕.兔类风湿性关节炎模型的诱导机制及组织病理学的研究[J].苏州大学学报(医学版),2005,25(5):63-66.
[11]龚爱迪,欧阳亚琳,张学英,等.国内外类风湿性关节炎动物实验模型研究进展分析[J].世界最新医学信息文摘,2015,15(19):25-27.
[12]刘永平,陈建双,赵波,等.赤雹根总皂苷对实验性佐剂型关节炎镇痛作用的研究[J].辽宁中医杂志,2011,38(8):1659-1661.
[13]晋小荣,朱苗苗,高永翔,等.TOLL样受体介导信号通路与类风湿关节炎关系的研究进展[J].湖南中医杂志,2017,33(10):193-195.
[14]陈利锋,刘辉,王华松,等.复方芪芎颗粒治疗类风湿性关节炎的机制[J].中国医院药学杂志,2017,37(20):2024-2028.
[15] GONG J, WEI T, STARK R W, et al. Inhibition of Toll-like receptors TLR4 and 7 signaling pathways by SIGIRR:A computational approach[J]. Journal of Structural Biology,2010,169(3):323-330.
[16] PARK S Y,LEE S W,BAEK S H,et al. Suppression of PU.1-linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis[J]. British Journal of Pharmacology,2013,168(6):1401-1411.
[17] CEREZO L A, REMAKOVA M, TOM IK M, et al.The metastasis-associated protein S100A4 promotes the inflammatory response of mononuclear cells via the TLR4 signalling pathway in rheumatoid arthritis[J].Rheumatology,2014,53(8):1520-1526.
[18] YAMAGUCHI R,SAKAMOTO A,YAMAMOTO T,et al. Differential regulation of IL-23 production in M1macrophages by TIR8/SIGIRR through TLR4-or TLR7/8-mediated signaling[J]. Cytokine,2017,99(11):310-315.
[19] KIM S, BANG J, SON C, et al. Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway[J].The Korean Journal of Internal Medicine,2016,33(3):612-621.
[20] RIVA F,BONAVITA E,BARBATI E,et al. TIR8/SIGIRR is an Interleukin-1 Receptor/Toll Like Receptor Family Member with Regulatory Functions in Inflammation and Immunity[J]. Front Immunol,2012,3(10):322-335.
[21] YAMAGUCHI R,SAKAMOTO A,YAMAGUCHI R,et al.Transcription factor specificity protein 1 modulates TGFbeta1/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P[J]. Cytokine,2018,108(8):24-36.
[22] BAUMAN T M, BECKA A J, SEHGAL P D, et al.SIGIRR/TIR8,an important regulator of TLR4 and IL-1R-mediated NF-kappaB activation,predicts biochemical recurrence after prostatectomy in low-grade prostate carcinomas[J]. Hum Pathol,2015,46(11):1744-1751.