人血丙种球蛋白和阿司匹林治疗对川崎病患儿循环内皮祖细胞功能的影响

徐明国; 门丽娜; 祖莹; 赵春玉; 孟祥春

PDF(1126 KB)

中国当代儿科杂志 ›› 2011, Vol. 13 ›› Issue (12) : 966-969.

论著·临床研究

人血丙种球蛋白和阿司匹林治疗对川崎病患儿循环内皮祖细胞功能的影响

徐明国，门丽娜，祖莹，赵春玉，孟祥春

作者信息 +

Effects of intravenous immunoglobulin and aspirin treatment on the functions of circulating endothelial progenitor cells in children with Kawasaki disease

XU Ming-Guo, MEN Li-Na, ZU Ying, ZHAO Chun-Yu, MENG Xiang-Chun

Author information +

文章历史 +

摘要

目的：研究人血丙种球蛋白(IVIG)和阿司匹林(ASP)治疗对川崎病患儿循环内皮祖细胞功能的影响及其可能的机制。方法：抽取10例川崎病患儿IVIG和ASP治疗前及治疗7 d后的外周血,将单个核细胞诱导培养内皮祖细胞。利用MTT法、改良Boyden小室法、细胞培养板贴壁法测定内皮祖细胞的增殖、迁移和贴壁功能。同时测定血浆中肿瘤坏死因子-α（TNF-α）和超敏C反应蛋白（hs-CRP）的浓度。结果：IVIG和ASP治疗7 d后循环内皮祖细胞的功能较治疗前显著提高。IVIG和ASP治疗7 d后血浆中TNF-α和hs-CRP 的浓度显著降低。治疗后TNF-α和hs-CRP 浓度的降低与内皮祖细胞功能的提高呈显著正相关关系。结论：IVIG和ASP治疗可显著改善川崎病患儿循环内皮祖细胞的功能，其机制可能与TNF-α和hs-CRP的浓度降低有关。

Abstract

OBJECTIVE: To study the effects of intravenous immunoglobulin (IVIG) and aspirin treatment on the functions of circulating endothelial progenitor cells (EPCs) in children with Kawasaki disease (KD) and possible mechanisms. METHODS: Blood samples were obtained in 10 children with KD before and 7 days after the treatment by IVIG and aspirin. MTT method, modified Boyden chamber method and cell culture plate adhesion method were used to assess the functions of EPCs, including proliferation, adhension and migration activities. The plasma levels of tumor necrosis factor-α (TNF-α) and high-sensitivity C reactive protein (hs-CRP) were also measured. RESULTS: The functions of circulating EPCs 7 days after IVIG and aspirin treatment were significantly improved. IVIG and aspirin treatment significantly reduced plasma TNF-α and hs-CRP concentrations. There was a significant linear regression relationship between the reduced plasma TNF-α and hs-CRP levels and the increased functions of circulating EPCs.ConclusionsIVIG and aspirin treatment can improve the functions of circulating EPCs, possibly through reducing plasma concentrations of TNF-α and hs-CRP.

导出引用

徐明国，门丽娜，祖莹，赵春玉，孟祥春. 人血丙种球蛋白和阿司匹林治疗对川崎病患儿循环内皮祖细胞功能的影响[J]. 中国当代儿科杂志. 2011, 13(12): 966-969

XU Ming-Guo, MEN Li-Na, ZU Ying, ZHAO Chun-Yu, MENG Xiang-Chun. Effects of intravenous immunoglobulin and aspirin treatment on the functions of circulating endothelial progenitor cells in children with Kawasaki disease[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(12): 966-969

中图分类号： R725

参考文献

［1］Brogan PA, Bose A, Burgner D, Shingadia D, Tulloh R, Michie C, et al. Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research［J］. Arch Dis Child, 2002, 86(4): 286-290.

［2］Furukawa S, Matsubara T, Ichiyama T. Regulation of proinflammatory cytokine cascade in Kawasaki disease［J］. Nippon Rinsho, 2008, 66(2): 258-264.

［3］Lau AC, Duong TT, Ito S, Wilson GJ, Yeung RS. Inhibition of matrix metalloproteinase-9 activity improves coronary outcome in an animal model of Kawasaki disease［J］. Clin Exp Immunol, 2009,157(2): 300-309.

［4］Lau AC, Duong TT, Ito S, Yeung RS. Intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki disease［J］. Arthritis Rheum, 2009, 60(7): 2131-2141.

［5］徐明国, 门丽娜, 王海霞, 祖莹, 赵春玉, 赵霞,等. 川崎病患儿循环内皮祖细胞功能与血浆超敏C反应蛋白浓度的关系［J］. 中国当代儿科杂志，2010，12(07)：513-517.

［6］Ahn SY, Jang GC, Shin JS, Shin KM, Kim DS. Tumor necrosis factor-alpha levels and promoter polymorphism in patients with Kawasaki disease in Korea［J］.Yonsei Med J, 2003, 44(6): 1021-1026.

［7］Mitani Y, Sawada H, Hayakawa H, Aoki K, Ohashi H, Matsumura M, et al. Elevated levels of high-sensitivity C-reactive protein and serum amyloid-A late after Kawasaki disease: association between inflammation and late coronary sequelae in Kawasaki disease［J］. Circulation, 2005, 111(1): 38-43.

［8］Pinna GS, Kafetzis DA, Tselkas OI, Skevaki CL. Kawasaki disease: an overview［J］.Curr Opin Infect Dis, 2008,21(3): 263-270.

［9］Chen J, Huang L, Song M, Yu S, Gao P, Jing J. C-reactive protein upregulates receptor for advanced glycation end products expression and alters antioxidant defenses in rat endothelial progenitor cells［J］. J Cardiovasc Pharmacol, 2009, 53(5): 359-367.

［10］Zhang Y, Herbert BS, Rajashekhar G, Ingram DA, Yoder MC, Clauss M, et al. Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor-alpha via the p38 mitogen-activated protein kinase pathway［J］. Faseb J, 2009, 23(5):1358-1365.

［11］Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis［J］. Science, 1997, 275(5302): 964-967.

［12］Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk［J］. N Engl J Med, 2003, 348(7): 593-600.

［13］Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes［J］. N Engl J Med, 2005, 353(10): 999-1007.

［14］于宪一. 川崎病的药物治疗［J］.中国处方药，2011，2（35）：21-23.

［15］Burns JC, Glode MP. Kawasaki syndrome［J］. Lancet, 2004, 364(9433): 533-544.

［16］Fukazawa R, Ogawa S. Long-term prognosis of patients with Kawasaki disease: at risk for future atherosclerosis?［J］. J Nippon Med Sch, 2009, 76(3): 124-133.

［17］蔡招华，刘亚黎.川崎病患者易早发动脉粥样硬化［J］.中国实用儿科学杂志，2011，26(9)：709-712.

［18］He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries［J］. Stroke, 2004, 35(10): 2378-2384.

［19］Werner N, Junk S, Laufs U, Link A, Walenta K, Bohm M, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury［J］. Circ Res, 2003, 93(2): e17-e24.

［20］Hui-Yuen JS, Duong TT, Yeung RS. TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease［J］. J Immunol, 2006, 176(10): 6294-6301.

［21］Musunuru K, Kral BG, Blumenthal RS, Fuster V, Campbell CY, Gluckman TJ, et al. The use of high-sensitivity assays for C-reactive protein in clinical practice［J］. Nat Clin Pract Cardiovasc Med, 2008, 5(10): 621-635.

［22］Nabata A, Kuroki M, Ueba H, Hashimoto S, Umemoto T, Wada H, et al. C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque［J］. Atherosclerosis, 2008, 196(1): 129-135.