托法替尼对克罗恩病小鼠血清炎症因子的作用及机制研究
|
摘要
目的研究托法替尼对克罗恩病小鼠模型血清炎症因子表达的影响及其机制。方法用2,4,6-三硝基苯磺酸钠(TNBS)建立克罗恩病小鼠模型。按照体重将造模成功小鼠分为3组:模型组和低、高2个剂量实验组,每组15只。模型组给予灌胃0. 9%NaCl;低、高2个剂量实验组分别灌胃托法替尼溶液30,60μg·mL~(-1)(均1 mL),均1次/天,连续5 d。用酶联免疫吸附法检测血清干扰素γ(IFN-γ)、白细胞介素6(IL-6)和白细胞介素17(IL-17)水平。结果模型组和低、高2个剂量实验组的血清中IFN-γ含量分别为(29. 12±1. 22),(20. 00±1. 14)和(14. 41±1. 06) pg·mg~(-1);上述3组的IL-6含量分别为(9. 00±1. 09),(7. 16±1. 32)和(5. 06±1. 15) pg·mg~(-1);上述3组的IL-17含量分别为(10. 11±1. 31),(8. 08±1. 21)和(5. 63±1. 10) pg·mg~(-1)。2个剂量实验组与模型组比较,上述指标的差异均有统计学意义(均P <0. 01);且实验组的效果与剂量呈正相关。结论托法替尼可抑制克罗恩病小鼠模型血清炎症因子分泌,减轻肠道炎症反应。
Objective To investigate the effect and mechanism of tofacitinib on serum inflammatory factors of Crohn 's disease in mice.Methods Crohn's disease mice model was induced by 2,4,6-three sodium nitrobenzene sulfonate( TNBS) intra-colonic administration.The model mice were randomly divided into three groups: model group,low and high dose of experimental groups,each group had 15 mice. Mice in model group were orally administered saline,while mice in experimental groups were orally administered with tofacitinib at the dose of 30,60μg· mL~(-1)( both 1 mL),respectively; once a day for consecutive 5 days. The level of interferonγ( IFN-γ),interleukin-6( IL-6) and interleukin-17( IL-17) in the serum were determined by enzyme linked immunosorbent assay. Results The serum IFN-γ content in model group,experimental-L group and experimental-H group were( 29. 12 ± 1. 22),( 20. 00 ± 1. 14),( 14. 41 ± 1. 06) pg·mg~(-1),respectively; the IL-6 content in the above three groups were( 9. 00 ± 1. 09),( 7. 16 ± 1. 32),( 5. 06 ± 1. 15) pg·mg~(-1),respectively; the IL-17 content in the above three groups were( 10. 11 ± 1. 31),( 8. 08 ± 1. 21),( 5. 63 ± 1. 10) pg·mg~(-1),respectively. Significant difference of the factors was found between the experimental groups and model group( all P < 0. 01). The effect of the experimental group was positively correlated with the dose. Conclusion Tofacitinib could inhibit the secretion of serum inflammatory cytokines and decrease colonic inflammation.
Objective To investigate the effect and mechanism of tofacitinib on serum inflammatory factors of Crohn 's disease in mice.Methods Crohn's disease mice model was induced by 2,4,6-three sodium nitrobenzene sulfonate( TNBS) intra-colonic administration.The model mice were randomly divided into three groups: model group,low and high dose of experimental groups,each group had 15 mice. Mice in model group were orally administered saline,while mice in experimental groups were orally administered with tofacitinib at the dose of 30,60μg· mL~(-1)( both 1 mL),respectively; once a day for consecutive 5 days. The level of interferonγ( IFN-γ),interleukin-6( IL-6) and interleukin-17( IL-17) in the serum were determined by enzyme linked immunosorbent assay. Results The serum IFN-γ content in model group,experimental-L group and experimental-H group were( 29. 12 ± 1. 22),( 20. 00 ± 1. 14),( 14. 41 ± 1. 06) pg·mg~(-1),respectively; the IL-6 content in the above three groups were( 9. 00 ± 1. 09),( 7. 16 ± 1. 32),( 5. 06 ± 1. 15) pg·mg~(-1),respectively; the IL-17 content in the above three groups were( 10. 11 ± 1. 31),( 8. 08 ± 1. 21),( 5. 63 ± 1. 10) pg·mg~(-1),respectively. Significant difference of the factors was found between the experimental groups and model group( all P < 0. 01). The effect of the experimental group was positively correlated with the dose. Conclusion Tofacitinib could inhibit the secretion of serum inflammatory cytokines and decrease colonic inflammation.
引文
[1] KLARESKOG L,WEDREN S,ALFREDSSON L. On the origins of complex immune-mediated disease:the example of rheumatoid arthritis[J]. J Mol Med,2009,89(4):357-362.
[2] KATSANOS K H,PAPADAKISK A. Inflammatory bowel disease:updates on molecular targets for biologics[J]. Gut Liver,2017,11(4):455-463.
[3] ZERBINI C A,LOMONTE A B. Tofacitinib for the treatment of rheumatoid arthritis[J]. Expert Rev Clin Immunol,2012,8(4):319-331.
[4] KARACA T,UZ Y H,DEMIRTAS S,et al. Protective effect of royal jelly in 2,4,6 trinitrobenzene sulfonic acid-induced colitis in rats[J]. Iran J Basic Med Sci,2015,18(4):370-379.
[5] ABDULL A H,ALI S,SALMAN M,et al. Dengue outbreaks in Khyber Pakhtunkhwa(KPK), pakistan in 2017:An integrated disease surveillance and response system(IDSRS)-based report[J]. Pol J Microbiol,2019,68(1):115-119.
[6] SAPORITI F,PIACENTINI L,ALFIERI V,et al. Melanocortin-1receptor positively regulates human artery endothelial cell migration[J]. Cell Physiol Biochem,2019,52(6):1339-1360.
[7] CIBOR D,SZCZEKLIK K,MACH T,et al. Levels of tissue factor pathway inhibitor in patients with inflammatory bowel disease[J].Pol Arch Intern Med,2019,129(4):253-258.
[8] MOTOYA S,WATANABE M,KIM H J,et al. Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis:subgroup analyses from three phase 3 multinational studies[J]. Intest Res,2018,16(2):233-245.
[9] DAI C,JIANG M,SUN M J. Tofacitinib as induction and maintenance therapy for ulcerative colitis[J]. N Engl J Med,2017,377(5):496-497.
[2] KATSANOS K H,PAPADAKISK A. Inflammatory bowel disease:updates on molecular targets for biologics[J]. Gut Liver,2017,11(4):455-463.
[3] ZERBINI C A,LOMONTE A B. Tofacitinib for the treatment of rheumatoid arthritis[J]. Expert Rev Clin Immunol,2012,8(4):319-331.
[4] KARACA T,UZ Y H,DEMIRTAS S,et al. Protective effect of royal jelly in 2,4,6 trinitrobenzene sulfonic acid-induced colitis in rats[J]. Iran J Basic Med Sci,2015,18(4):370-379.
[5] ABDULL A H,ALI S,SALMAN M,et al. Dengue outbreaks in Khyber Pakhtunkhwa(KPK), pakistan in 2017:An integrated disease surveillance and response system(IDSRS)-based report[J]. Pol J Microbiol,2019,68(1):115-119.
[6] SAPORITI F,PIACENTINI L,ALFIERI V,et al. Melanocortin-1receptor positively regulates human artery endothelial cell migration[J]. Cell Physiol Biochem,2019,52(6):1339-1360.
[7] CIBOR D,SZCZEKLIK K,MACH T,et al. Levels of tissue factor pathway inhibitor in patients with inflammatory bowel disease[J].Pol Arch Intern Med,2019,129(4):253-258.
[8] MOTOYA S,WATANABE M,KIM H J,et al. Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis:subgroup analyses from three phase 3 multinational studies[J]. Intest Res,2018,16(2):233-245.
[9] DAI C,JIANG M,SUN M J. Tofacitinib as induction and maintenance therapy for ulcerative colitis[J]. N Engl J Med,2017,377(5):496-497.