补肾益髓胶囊对视神经脊髓炎患者缓解期BAFF、CXCL13及IL-6的影响
|
摘要
目的观察补肾益髓胶囊治疗神经脊髓炎(NMO)患者的临床疗效及其对外周血B细胞活化因子(BAFF)、趋化因子配体(CXCL) 13及白细胞介素(IL) 6表达的影响。方法缓解期NMO患者26例,使用补肾益髓胶囊治疗3个月。同时招募健康志愿者22例作为对照。比较患者服药前后扩展残疾状态量表(EDSS)评分、中医症状评分以及B细胞相关细胞因子表达水平的变化。结果经补肾益髓胶囊治疗后,缓解期NMO患者的EDSS评分、中医症状评分较治疗前明显降低(P <0. 05,P <0. 01),外周血IL-6表达水平显著降低(P <0. 01),BAFF和CXCL13表达水平变化差异无统计学意义(P> 0. 05)。缓解期NMO患者血清CXCL13的表达水平较健康组明显升高(P=0. 000),BAFF表达水平与健康组比较差异无统计学意义(P=0. 197),缓解期NMO患者血清IL-6表达水平较健康组明显升高(P=0. 009)。结论补肾益髓胶囊可以显著改善缓解期NMO患者的神经功能缺损症状,可能与其能够有效降低缓解期NMO患者血清IL-6表达水平有关。
Objective To observe clinical efficacy of Bushenyisui Capsules in treatment of the remission period of patients with optic neuromyelitis( NMO) and its effect on levels of BAFF,CXCL13 and IL-6. Methods 26 patients with NMO during remission were treated with Bushen Yisui Capsule for 3 months. At the same time,22 healthy volunteers were recruited as controls. The changes of the Extended Disability Status Scale( EDSS) score,TCM symptom score,and B cell-associated cytokine expression levels before and after treatment were compared. Results After treatment with Bushen Yisui Capsule,the EDSS score and TCM symptom score of NMO patients during the remission period were significantly lower than those before treatment( P < 0. 05,P < 0. 01),and the expression of IL-6 in peripheral blood was significantly decreased( P < 0. 01). There was no significant difference in the expression level of BAFF and CXCL13 before and after treatment( P > 0. 05). The expression level of CXCL13 in NMO patients was significantly higher than that in healthy group( P = 0. 000). There was no significant difference in the expression level of BAFF expression between NMO patients and healthy person( P = 0. 197). The expression of serum IL-6 in NMO patients during remission period was higher than that in healthy group( P = 0. 009). Conclusion Bushen Yisui Capsule can significantly improve the symptoms of neurological deficits in patients with NMO during remission,which may be related to its ability to effectively reduce the level of serum IL-6.
Objective To observe clinical efficacy of Bushenyisui Capsules in treatment of the remission period of patients with optic neuromyelitis( NMO) and its effect on levels of BAFF,CXCL13 and IL-6. Methods 26 patients with NMO during remission were treated with Bushen Yisui Capsule for 3 months. At the same time,22 healthy volunteers were recruited as controls. The changes of the Extended Disability Status Scale( EDSS) score,TCM symptom score,and B cell-associated cytokine expression levels before and after treatment were compared. Results After treatment with Bushen Yisui Capsule,the EDSS score and TCM symptom score of NMO patients during the remission period were significantly lower than those before treatment( P < 0. 05,P < 0. 01),and the expression of IL-6 in peripheral blood was significantly decreased( P < 0. 01). There was no significant difference in the expression level of BAFF and CXCL13 before and after treatment( P > 0. 05). The expression level of CXCL13 in NMO patients was significantly higher than that in healthy group( P = 0. 000). There was no significant difference in the expression level of BAFF expression between NMO patients and healthy person( P = 0. 197). The expression of serum IL-6 in NMO patients during remission period was higher than that in healthy group( P = 0. 009). Conclusion Bushen Yisui Capsule can significantly improve the symptoms of neurological deficits in patients with NMO during remission,which may be related to its ability to effectively reduce the level of serum IL-6.
引文
[1]Lennon VA,Wingerchuk DM,Kryzer TJ,et al. A serum autoantibody marker of neuromyelitis optica:distinction from multiple sclerosis[J]. Lancet,2004,364(9451):2106-2112.
[2]Takahashi T,Fujihara K,Nakashima I,et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO:a study on antibody titter[J]. Brain,2007,130(Pt 5):1235-1243.
[3]Morita R,Schmitt N,Bentebibel SE,et al. Human blood CXCR5+CD4+T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion[J]. Immunity,2011. 34(1):108-121.
[4]Avery DT,Kalled SL,Ellyard JI,et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells[J]. J Clin Invest,2003,112(2):286-297.
[5]Wingerchuk DM,Lennon VA,Pittock SJ,et al. Revised diagnostic criteria for neuromyelitis optica[J]. Neurology,2006,66(10):1485-1489.
[6]王苏.补肾益髓胶囊对视神经脊髓炎缓解期临床疗效及体液免疫功能的影响[D].北京:北京中医药大学,2015.
[7]樊永平,胡蕊,鲍显慧,等. 63例视神经脊髓炎患者临床特点和中医证型分布[J].中国中西医结合杂志,2013(3):322-325.
[8]王苏,樊永平,张永超,等.不同中医证型视神经脊髓炎患者临床特点比较[J].环球中医药,2014(11):833-835.
[9]王苏,樊永平,张永超,等.中医辨证论治对视神经脊髓炎年复发率影响的临床观察[J].中华中医药杂志,2014,(12):3814-3816.
[10]Lennon VA,Kryzer TJ,Pittock SJ,et al. Ig G marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel[J]. J Exp Med,2005,202(4):473-477.
[11]安云庆,姚智.医学免疫学[M].北京:北京大学医学出版社,2013:91.
[12]Zhong X,Wang H,Dai Y,et al. Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica[J]. J Neuroimmunol,2011(240):104-108.
[13]Quan C,Yu H,Qiao J,et al. Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica:distinct from multiple sclerosis[J]. Mult Scler,2013,19(3):289-298.
[14]Hase H,Kanno Y,Kojima M,et al. BAFF/BLyS can potentiate Bcell selection with the B-cell coreceptor complex[J]. Blood,2004,103(6):2257-2265.
[15]Okada K,Matsushita T,Kira J,et al. B-cell activating factor of the TNF family is upregulated in neuromyelitis optica[J]. Neurology,2010,74(2):177-178.
[16]Uzawa A,Mori M,Arai K,et al. Cytokine and chemokine profiles in neuromyelitis optica:significance of interleukin-6[J]. Mult Scler,2010,16(12):1443-1452.
[17]Chihara N,Aranami T,Sato W,et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica[J]. Proc Natl Acad Sci USA,2011,108(9):3701-3706.
[18]Alvarez E,Piccio L,Mikesell RJ,et al. CXCL13 is a biomarker of inflammation in multiple sclerosis,neuromyelitis optica,and other neurological conditions[J]. Mult Scler,2013,19(9):1204-1208.
[19]Krumbholz M,Meinl E. B cells in MS and NMO:pathogenesis and therapy[J]. Semin Immunopathol,2014,36(3):339-350.
[20]Wang S,Yang T,Wan J,et al. Elevated C-X-C motifligand 13and B-cell-activating factor levels in neuromyelitis optica during remission[J]. Brain Behav,2017,7(4):e00 648.
[21]Maeda K,Mehta H,Drevets DA,Coggeshall KM. IL-6 increases B-cell Ig G production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production[J]. Blood,2010,115(23):4699-4706.
[22]Iz S,Tüzün E,KürtüncüM,et al. Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients[J]. Int J Neurosci,2010,120(1):71-75.
[2]Takahashi T,Fujihara K,Nakashima I,et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO:a study on antibody titter[J]. Brain,2007,130(Pt 5):1235-1243.
[3]Morita R,Schmitt N,Bentebibel SE,et al. Human blood CXCR5+CD4+T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion[J]. Immunity,2011. 34(1):108-121.
[4]Avery DT,Kalled SL,Ellyard JI,et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells[J]. J Clin Invest,2003,112(2):286-297.
[5]Wingerchuk DM,Lennon VA,Pittock SJ,et al. Revised diagnostic criteria for neuromyelitis optica[J]. Neurology,2006,66(10):1485-1489.
[6]王苏.补肾益髓胶囊对视神经脊髓炎缓解期临床疗效及体液免疫功能的影响[D].北京:北京中医药大学,2015.
[7]樊永平,胡蕊,鲍显慧,等. 63例视神经脊髓炎患者临床特点和中医证型分布[J].中国中西医结合杂志,2013(3):322-325.
[8]王苏,樊永平,张永超,等.不同中医证型视神经脊髓炎患者临床特点比较[J].环球中医药,2014(11):833-835.
[9]王苏,樊永平,张永超,等.中医辨证论治对视神经脊髓炎年复发率影响的临床观察[J].中华中医药杂志,2014,(12):3814-3816.
[10]Lennon VA,Kryzer TJ,Pittock SJ,et al. Ig G marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel[J]. J Exp Med,2005,202(4):473-477.
[11]安云庆,姚智.医学免疫学[M].北京:北京大学医学出版社,2013:91.
[12]Zhong X,Wang H,Dai Y,et al. Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica[J]. J Neuroimmunol,2011(240):104-108.
[13]Quan C,Yu H,Qiao J,et al. Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica:distinct from multiple sclerosis[J]. Mult Scler,2013,19(3):289-298.
[14]Hase H,Kanno Y,Kojima M,et al. BAFF/BLyS can potentiate Bcell selection with the B-cell coreceptor complex[J]. Blood,2004,103(6):2257-2265.
[15]Okada K,Matsushita T,Kira J,et al. B-cell activating factor of the TNF family is upregulated in neuromyelitis optica[J]. Neurology,2010,74(2):177-178.
[16]Uzawa A,Mori M,Arai K,et al. Cytokine and chemokine profiles in neuromyelitis optica:significance of interleukin-6[J]. Mult Scler,2010,16(12):1443-1452.
[17]Chihara N,Aranami T,Sato W,et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica[J]. Proc Natl Acad Sci USA,2011,108(9):3701-3706.
[18]Alvarez E,Piccio L,Mikesell RJ,et al. CXCL13 is a biomarker of inflammation in multiple sclerosis,neuromyelitis optica,and other neurological conditions[J]. Mult Scler,2013,19(9):1204-1208.
[19]Krumbholz M,Meinl E. B cells in MS and NMO:pathogenesis and therapy[J]. Semin Immunopathol,2014,36(3):339-350.
[20]Wang S,Yang T,Wan J,et al. Elevated C-X-C motifligand 13and B-cell-activating factor levels in neuromyelitis optica during remission[J]. Brain Behav,2017,7(4):e00 648.
[21]Maeda K,Mehta H,Drevets DA,Coggeshall KM. IL-6 increases B-cell Ig G production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production[J]. Blood,2010,115(23):4699-4706.
[22]Iz S,Tüzün E,KürtüncüM,et al. Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients[J]. Int J Neurosci,2010,120(1):71-75.