EGCG及氟伐他汀抑制anti-β2GPI/β2GPI复合物诱导的THP-1细胞活化
|
摘要
研究目的：
β2糖蛋白I (beta-2-glycoproteinI, β2GPI)与其相应抗体(抗β2GPI, anti-β2GPI)形成复合物,能够刺激血液单核细胞、血管内皮细胞活化,表达相关细胞因子,参与抗磷脂综合征(antiphospholipid syndrome, APS)的高凝状态和炎性反应,是其重要的病理机制之一。课题组前期研究揭示,在anti-β2GPI/β2GPI复合物刺激人单核细胞株THP-1表达组织因子(tissue factor, TF)的过程中,跨膜蛋白Toll样受体4(Toll-like receptor4, TLR4)及其下游信号转导分子能够被诱导表达并参与细胞的激活作用,并且部分依赖膜联蛋白Ⅱ (Annexin A2, ANX2),成为APS血栓形成的机制之一。本论文旨在前期研究基础上,以TF和肿瘤坏死因子-α (tumor necrosis factor, TNF-a)为指标,探讨绿茶中重要的活性成分表没食子儿茶素-3-没食子酸酯(epigallocatechin-3-gallate, EGCG)以及他汀类之一的氟伐他汀能否抑制mti-β2GPI/β2GPI复合物介导的单核细胞株THP-1活化,其具体分子机制如何,为APS预防和治疗提供新的思路。
研究方法：
(1)利用实时定量PCR (Real-time quantitative PCR, RT-qPCR)检测anti-β2GPI/β2GPI复合物诱导THP-1细胞TF和TNF-α mRNA的表达,采用试剂盒检测TF活性,ELISA试剂盒检测TNF-a蛋白含量。
(2)采用不同浓度的EGCG和氟伐他汀预处理THP-1细胞,MTT法观察对细胞增殖活力的影响。
(3)观察不同浓度的EGCG和氟伐他汀对anti-β2GPI/β2GPI复合物诱导THP-1细胞表达TF和TNF-a的抑制作用,并检测其量效性和特异性。
(4)运用RT-qPCR和Western blotting方法检测EGCG和氟伐他汀对anti-β2GPI/β2GPI复合物诱导的THP-1细胞TLR4mRNA和蛋白表达的抑制作用。
(5) Western blotting检测anti-β2GPI/β2GPI复合物刺激THP-1细胞有丝分裂原蛋白激酶(mitogen-activated protein kinases, MAPKs)与核因子κB (nuclear factor kappa B, NF-κB)的活化情况,并检测刺激的时效性。
(6)采用不同浓度的EGCG和氟伐他汀预处理THP-1细胞,观察其对anti-β/β2GPI复合物诱导THP-1细胞MAPKs和NF-κB p65表达和磷酸化的干预作用,并检测其量效性。
研究结果：
(1) Anti-β2GPI/β2GPI复合物能够刺激THP-1细胞表达TF (mRNA及活性)和TNF-α (mRNA及蛋白),与对照组相比,差异显著(p<0.05)。
(2)较低浓度的EGCG和氟伐他汀不影响THP-1细胞增殖活力。当EGCG浓度为100μg/ml,氟伐他汀浓度为50μg/ml时,可以显著抑制THP-1细胞增殖(p<0.05)。
(3) EGCG和氟伐他汀抑制anti-β2GPI/β2GPI复合物对THP-1细胞TF和TNF-α表达的刺激效应,并呈现浓度依赖性。
(4) Anti-β2GPI/β2GPI复合物刺激THP-1细胞后,TLR4表达增高；EGCG和氟伐他汀可以抑制anti-β2GPI/β2GPI复合物诱导的THP-1细胞TLR4mRNA和蛋白表达。
(5) Anti-β2GPI/β2GPI复合物刺激THP-1细胞表达TF和TNF-α,同时增加THP-1细胞MAPKs和NF-κB的磷酸化水平,并显示时间效应。EGCG和氟伐他汀显著抑制anti-β2GPI/β2GPI复合物诱导的THP-1细胞MAPKs (ERK1/2、JNK、p38)和NF-κB的磷酸化(p<0.05),并呈现一定的浓度依赖性。
结论：
(1) Anti-β2GPI/β2GPI复合物能够刺激单核细胞THP-1活化,使细胞表达TF及TNF-α显著增加。
(2) EGCG和氟伐他汀能抑制anti-β2GPI/β2GPI复合物对THP-1细胞TF和TNF-α表达的刺激效应。
(3) EGCG和氟伐他汀干预anti-β2GPI/β2GPI复合物刺激的TLR4表达增强,以及MAPKs和NF-κB的磷酸化。
(4) EGCG和氟伐他汀通过抑制TLR4-MAPKs-NF-κB信号通路,干预anti-β2GPI/β2GPI复合物对THP-1细胞的活化,提示可用于APS血栓形成的预防及治疗。
Objective:
Anti-β2-glycoproteinI/β2-glycoproteinI (anti-β2GPI/β2GPI) complex could activate endothelial cells and monocytes upon binding to the surface membrane of the cells, enhancing the expression and secretion of many cytokines, thereby increasing the risk of thrombosis, which are beneficial to the thrombus formation of antiphospholipid syndrome (APS). Our previous study reveals that the Toll-like receptor4(TLR4) and its signal transduction pathway can be induced to express and participate in cellular activation, and the effects of TLR4with annexinA2(ANX2) are tightly cooperative in process of anti-β2GPI/β2GPI-stimulated tissue factor (TF) and tumor necrosis factor-a (TNF-a) expression in the human monocytic cell line THP-1. These may be responsible for the thrombotic mechanisms in APS. In the present study, we investigated the effects of EGCG (epigallocatechin-3-gallate) and fluvastatin on anti-β2GPI/β2GPI complex-induced THP-1cells activation, targeting to the expression of TF and TNF-a, as well as the possible mechanisms involved in this process. The study may provide a new way for prevention and treatment of thrombotic issues in APS.
Methods:
(1) The THP-1cells were treated with anti-β2GPI/β2GPI complex. The TF and TNF-a mRNA expression on cells were detected by Real-time quantitative PCR (RT-qPCR), the TF activity and TNF-α protein level were estimated by commercial kits respectively.
(2) Pretreated with different concentration of EGCG or fluvastatin, the cell proliferation ability was detected by MTT assay.
(3) Pretreated with different concentration of EGCG or fluvastatin, the levels of TF and TNF-a induced by anti-β2GPI/β2GPI complex were examined by RT-qPCR and commercial kits respectively. The dose course and specific effects of EGCG or fluvastatin on THP-1cells were also investigated.
(4) EGCG and fluvastatin were used to investigate whether the TLR4expression (mRNA and protein) in cells induced by anti-β2GPI/β2GPI could be intervened.
(5) The phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in THP-1cells induced by anti-β2GPI/β2GPI complex were investigated by western blotting. The time course of anti-β2GPI/β2GPI complex in cells was also investigated.
(6) EGCG and fluvastatin were used to investigate whether the phosphorylation of NF-κB and MAPKs in cells induced by anti-β2GPI/β2GPI could be decreased by western blot assays, the dose course in THP-1cells was also investigated.
Results:
(1) The TF and TNF-α expression in THP-1cells were significantly up-regulated with treatment of anti-β2GPI/β2GPI complex, compared with untreated cells (p<0.05).
(2) High concentration of EGCG (100μg/ml) or fluvastatin (50μg/ml) could inhibit cell proliferation in THP-1cells.
(3) EGCG and fluvastatin could dose-dependently decrease TF and TNF-a level in THP-1cells stimulated with anti-β2GPI/β2GPI complex.
(4) The expression of TLR4was significantly increased with stimulation of anti-β2GPI/β2GPI complex. EGCG and fluvastatin reduced anti-β2GPI/β2GPI complex-enhanced TLR4mRNA and its protein levels.
(5) The phosphorylation of NF-κB and MAPKs in THP-1cells were also significantly increased with stimulation of anti-β2GPI/β2GPI complex, in a manner of time-dependence. EGCG and fluvastatin dose-dependently decrease phosphorylation of NF-κB and MAPKs in the presence of anti-β2GPI/β2GPI (p<0.05).
Conclusions:
(1) The TF and TNF-a expression in THP-1cells can be significantly up-regulated with treatment of anti-β2GPI/β2GPI complex.
(2) EGCG and fluvastatin can decrease anti-β2GPI/β2GPI-induced TF and TNF-a expression in THP-1cells.
(3) EGCG and fluvastatin can reduce the expression of TLR4, phosphorylation of NF-κB and MAPKs in the presence of anti-β2GPI/β2GPI complex.
(4) EGCG and fluvastatin attenuate anti-β2GPI/β2GPI-induced activation in THP-1cells through inhibiting the intracellular signal transduction pathway of TLR4-MAPKs-NF-κB axis and may serve as preventive and therapeutic agents for APS.
β2糖蛋白I (beta-2-glycoproteinI, β2GPI)与其相应抗体(抗β2GPI, anti-β2GPI)形成复合物,能够刺激血液单核细胞、血管内皮细胞活化,表达相关细胞因子,参与抗磷脂综合征(antiphospholipid syndrome, APS)的高凝状态和炎性反应,是其重要的病理机制之一。课题组前期研究揭示,在anti-β2GPI/β2GPI复合物刺激人单核细胞株THP-1表达组织因子(tissue factor, TF)的过程中,跨膜蛋白Toll样受体4(Toll-like receptor4, TLR4)及其下游信号转导分子能够被诱导表达并参与细胞的激活作用,并且部分依赖膜联蛋白Ⅱ (Annexin A2, ANX2),成为APS血栓形成的机制之一。本论文旨在前期研究基础上,以TF和肿瘤坏死因子-α (tumor necrosis factor, TNF-a)为指标,探讨绿茶中重要的活性成分表没食子儿茶素-3-没食子酸酯(epigallocatechin-3-gallate, EGCG)以及他汀类之一的氟伐他汀能否抑制mti-β2GPI/β2GPI复合物介导的单核细胞株THP-1活化,其具体分子机制如何,为APS预防和治疗提供新的思路。
研究方法：
(1)利用实时定量PCR (Real-time quantitative PCR, RT-qPCR)检测anti-β2GPI/β2GPI复合物诱导THP-1细胞TF和TNF-α mRNA的表达,采用试剂盒检测TF活性,ELISA试剂盒检测TNF-a蛋白含量。
(2)采用不同浓度的EGCG和氟伐他汀预处理THP-1细胞,MTT法观察对细胞增殖活力的影响。
(3)观察不同浓度的EGCG和氟伐他汀对anti-β2GPI/β2GPI复合物诱导THP-1细胞表达TF和TNF-a的抑制作用,并检测其量效性和特异性。
(4)运用RT-qPCR和Western blotting方法检测EGCG和氟伐他汀对anti-β2GPI/β2GPI复合物诱导的THP-1细胞TLR4mRNA和蛋白表达的抑制作用。
(5) Western blotting检测anti-β2GPI/β2GPI复合物刺激THP-1细胞有丝分裂原蛋白激酶(mitogen-activated protein kinases, MAPKs)与核因子κB (nuclear factor kappa B, NF-κB)的活化情况,并检测刺激的时效性。
(6)采用不同浓度的EGCG和氟伐他汀预处理THP-1细胞,观察其对anti-β/β2GPI复合物诱导THP-1细胞MAPKs和NF-κB p65表达和磷酸化的干预作用,并检测其量效性。
研究结果：
(1) Anti-β2GPI/β2GPI复合物能够刺激THP-1细胞表达TF (mRNA及活性)和TNF-α (mRNA及蛋白),与对照组相比,差异显著(p<0.05)。
(2)较低浓度的EGCG和氟伐他汀不影响THP-1细胞增殖活力。当EGCG浓度为100μg/ml,氟伐他汀浓度为50μg/ml时,可以显著抑制THP-1细胞增殖(p<0.05)。
(3) EGCG和氟伐他汀抑制anti-β2GPI/β2GPI复合物对THP-1细胞TF和TNF-α表达的刺激效应,并呈现浓度依赖性。
(4) Anti-β2GPI/β2GPI复合物刺激THP-1细胞后,TLR4表达增高；EGCG和氟伐他汀可以抑制anti-β2GPI/β2GPI复合物诱导的THP-1细胞TLR4mRNA和蛋白表达。
(5) Anti-β2GPI/β2GPI复合物刺激THP-1细胞表达TF和TNF-α,同时增加THP-1细胞MAPKs和NF-κB的磷酸化水平,并显示时间效应。EGCG和氟伐他汀显著抑制anti-β2GPI/β2GPI复合物诱导的THP-1细胞MAPKs (ERK1/2、JNK、p38)和NF-κB的磷酸化(p<0.05),并呈现一定的浓度依赖性。
结论：
(1) Anti-β2GPI/β2GPI复合物能够刺激单核细胞THP-1活化,使细胞表达TF及TNF-α显著增加。
(2) EGCG和氟伐他汀能抑制anti-β2GPI/β2GPI复合物对THP-1细胞TF和TNF-α表达的刺激效应。
(3) EGCG和氟伐他汀干预anti-β2GPI/β2GPI复合物刺激的TLR4表达增强,以及MAPKs和NF-κB的磷酸化。
(4) EGCG和氟伐他汀通过抑制TLR4-MAPKs-NF-κB信号通路,干预anti-β2GPI/β2GPI复合物对THP-1细胞的活化,提示可用于APS血栓形成的预防及治疗。
Objective:
Anti-β2-glycoproteinI/β2-glycoproteinI (anti-β2GPI/β2GPI) complex could activate endothelial cells and monocytes upon binding to the surface membrane of the cells, enhancing the expression and secretion of many cytokines, thereby increasing the risk of thrombosis, which are beneficial to the thrombus formation of antiphospholipid syndrome (APS). Our previous study reveals that the Toll-like receptor4(TLR4) and its signal transduction pathway can be induced to express and participate in cellular activation, and the effects of TLR4with annexinA2(ANX2) are tightly cooperative in process of anti-β2GPI/β2GPI-stimulated tissue factor (TF) and tumor necrosis factor-a (TNF-a) expression in the human monocytic cell line THP-1. These may be responsible for the thrombotic mechanisms in APS. In the present study, we investigated the effects of EGCG (epigallocatechin-3-gallate) and fluvastatin on anti-β2GPI/β2GPI complex-induced THP-1cells activation, targeting to the expression of TF and TNF-a, as well as the possible mechanisms involved in this process. The study may provide a new way for prevention and treatment of thrombotic issues in APS.
Methods:
(1) The THP-1cells were treated with anti-β2GPI/β2GPI complex. The TF and TNF-a mRNA expression on cells were detected by Real-time quantitative PCR (RT-qPCR), the TF activity and TNF-α protein level were estimated by commercial kits respectively.
(2) Pretreated with different concentration of EGCG or fluvastatin, the cell proliferation ability was detected by MTT assay.
(3) Pretreated with different concentration of EGCG or fluvastatin, the levels of TF and TNF-a induced by anti-β2GPI/β2GPI complex were examined by RT-qPCR and commercial kits respectively. The dose course and specific effects of EGCG or fluvastatin on THP-1cells were also investigated.
(4) EGCG and fluvastatin were used to investigate whether the TLR4expression (mRNA and protein) in cells induced by anti-β2GPI/β2GPI could be intervened.
(5) The phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in THP-1cells induced by anti-β2GPI/β2GPI complex were investigated by western blotting. The time course of anti-β2GPI/β2GPI complex in cells was also investigated.
(6) EGCG and fluvastatin were used to investigate whether the phosphorylation of NF-κB and MAPKs in cells induced by anti-β2GPI/β2GPI could be decreased by western blot assays, the dose course in THP-1cells was also investigated.
Results:
(1) The TF and TNF-α expression in THP-1cells were significantly up-regulated with treatment of anti-β2GPI/β2GPI complex, compared with untreated cells (p<0.05).
(2) High concentration of EGCG (100μg/ml) or fluvastatin (50μg/ml) could inhibit cell proliferation in THP-1cells.
(3) EGCG and fluvastatin could dose-dependently decrease TF and TNF-a level in THP-1cells stimulated with anti-β2GPI/β2GPI complex.
(4) The expression of TLR4was significantly increased with stimulation of anti-β2GPI/β2GPI complex. EGCG and fluvastatin reduced anti-β2GPI/β2GPI complex-enhanced TLR4mRNA and its protein levels.
(5) The phosphorylation of NF-κB and MAPKs in THP-1cells were also significantly increased with stimulation of anti-β2GPI/β2GPI complex, in a manner of time-dependence. EGCG and fluvastatin dose-dependently decrease phosphorylation of NF-κB and MAPKs in the presence of anti-β2GPI/β2GPI (p<0.05).
Conclusions:
(1) The TF and TNF-a expression in THP-1cells can be significantly up-regulated with treatment of anti-β2GPI/β2GPI complex.
(2) EGCG and fluvastatin can decrease anti-β2GPI/β2GPI-induced TF and TNF-a expression in THP-1cells.
(3) EGCG and fluvastatin can reduce the expression of TLR4, phosphorylation of NF-κB and MAPKs in the presence of anti-β2GPI/β2GPI complex.
(4) EGCG and fluvastatin attenuate anti-β2GPI/β2GPI-induced activation in THP-1cells through inhibiting the intracellular signal transduction pathway of TLR4-MAPKs-NF-κB axis and may serve as preventive and therapeutic agents for APS.
引文
[1]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) [J]. Thromb Haemost,2006,4(2):295-306.
[2]陈晓微,申艳,杨程德等.抗磷脂综合征174例临床特点及与欧洲数据的比较分析[J].中华风湿病学杂志,2010,14(6)：394-397.
[3]Avalos I, Tsokos GC. The role of complement in the antiphospholipid syndrome-associated pathology [J]. Clin Rev Allergy Immunol,2009,36 (1):141-144.
[4]Hedge VA, Vivas Y, Shah H, et al. Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome-a case series [J]. Heart Lung Circ,2007, 16(6):423-437.
[5]Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies [J]. Arthritis Rheum,2012, 64(7):2311-2318.
[6]McNeil HP, Simpson RJ, Chesterman CN, et al. Antiphospholipid antibodies are directed against a complex antigen that induces a lipid-binding inhibitor of coagulant:β2-glycoprotein Ⅰ [J]. Proc Natl Acid,1990,87(7):4120-4124.
[7]Willis R, Pierangeli SS. Anti-β2-glycoprotein I antibodies [J]. Ann N Y Acad Sci,2013,1285(5):44-58.
[8]Nojima J, Kuratsune H, Suehisa E, et al. Association between the prevalence of antibodies to beta 2-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications [J]. Clin Chem,2001,47(7):1008-1015.
[9]Zhou H, Wolberg AS, Roubey RA. Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep [J]. Blood,2004,104(8):2353-2358.
[10]Rahgozar S. Revisiting Beta 2 glycoprotein I, the major autoantigen in the antiphospholipid syndrome [J]. Iran J Immunol,2012,9(2):73-85.
[11]Levine JS, Branch DW, Rauch J.The antiphospholipid syndrome [J]. N Engl Med,2002,346(10):752-763.
[12]Singh NK, Behera DR, Agrawal, A et al. Hospital based prospective longitudinal clinical and immunologic study of 179 patients of primary anti-phospholipid syndrome [J]. Int J Rheum Dis,2013,16(5):547-547.
[13]Blank M, Krause I, Fridkin M, et al. Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome [J]. Clin Invest,2002,109(6):797-804.
[14]Sene D, Piette JC, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and infections [J]. Autoimmun Rev,2008,7(4):272-277.
[15]Cabiedes J, Cabral AR. Anti-beta2-glycoprotein-Ⅰ antibodies in sc Fv format [J]. Autoimmun Rev,2005,4(5):289-295.
[16]GiannakoPoulos B, Passam F, Rahgozar S, et al. Current concepts on the pathogenesis of the antiphospholipid syndrome [J]. Blood,2007, 109(2):422-430.
[17]Matsuura E, Lopez LR, Shoenfeld Y, et al. β2-glycoprotein I and oxidative inflammation in early atherogenesis:a progression from innate to adaptive immunity? [J]. Autoimmun Rev,2012,12(2):241-249.
[18]Stojanovich L, Kontic M, Smiljanic D, et al. Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid syndrome [J]. Clin Exp Rheumatol,2013,31(5):756-60.
[19]Raby A, Moffat K, Crowther M. Anticardiolipin antibody and anti-beta 2 glycoprotein I antibody assays [J]. Methods Mol Biol,2013,992:387-405..
[20]杨朝东,史伟雄,夏健,等.β2-糖蛋白Ⅰ与脑卒中关系的研究[J].中华内科杂志,2003,42(3)：192-193.
[21]Groot PG, Meijers JC. β(2)-Glycoprotein Ⅰ:evolution, structure and function [J]. Thromb Haemost,2011,9(7):1275-1284.
[22]Roubey RA. Immunology of the antiphospholipid syndrome:antibodies, antigens, and antiimmune response [J].Thromb Haemost,1999,82(2):656-661.
[23]MeNeeley PA, Dlott JS, Furie RA, et al. beta2-glycoprotein-dependent anficardiolipin antibodies pref-erentially bind the amino terminal domain of beta 2-glycoproteinl [J]. Thromb Haemost,2001,86(2):590-595.
[24]Blank M, Shoenfeld Y, Cabilly S, et al. Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides [J]. ProcNatl Acad Sci USA,1999,96(9):5164-5168.
[25]Yang CD, Chen SL, Shen N, et al. Deteetion of antirecombint beta 2-glycoprotein fifth-domain antibodies in sera from patients with systemic lupus erythematosus [J]. Rheumatol Int,1998,18(1):5-10.
[26]Basde LH, Derksen RH, deGroot PG. Beta2-glycoprotein 1, the Playmaker of the antiphospholipid syndrome [J].Clin Immunol,2004,112(2):161-168.
[27]Sciascia S, Sanna G, Murru V, et al. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome, a systematic review [J]. Thromb Haemost,2013,111 (2):epub.
[28]Ghirardello A, Bizzaro N, Zampieri S, et al. Biological and clinical relevance of anti-prothrombin antibodies [J]. Ann NY Acad Sci,2007,1109(4):503-510.
[29]Jaskowski TD, Wilson AR, Hill HR, et al. Autoantibodies against phosphatidylserine, prothrombin and phosphatidylserine-prothrombin complex:identical or distinct diagnostic tools for antiphospholipid syndrome [J]. Clin Chim Aeta,2009,4(10):19-24.
[30]Pengo V, Denas G, Bison E, et al. On behalf of participating centers of Italian Federation of Thrombosis Centers (FCSA). Prevalence and siginificance of anti-prothrombin (aPT) antibodies in patients with lupus anticoagulant (LA) [J]. Thromb Res,2010,126(2):150-3.
[31]Sakai Y, Atsumi T, Ieko M, et al. The effects of phosphatidylserine-dependent antiprothrombin antibody on thrombingen-eration [J]. Arthritis Rheum,2009,60(8):2457-67.
[32]Rand JH, Wu XX, Andree HA, et al. Pregnancy loss in the antiphospholipid-antibody syndrome -a possible thromobogenic mechanism [J]. N Engl J Med,1997,337 (3):154-160.
[33]Singh NK, Yadav DP, Gupta A, et al. Role of anti-annexin A5 in pathogenesis of hypercoagulable state in patients with antiphospholipid syndrome [J]. Int J Rheum Dis,2013,16(3):325-30.
[34]Pierangeli SS, Espinola RG, Liu X, et al. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1 Vascular cell adhesion molecule-1, and p-selectin [J]. Cire Res,2001, 88(2):245-50.
[35]Forastiero RR, Martinuzzo ME, delarranaga GF. Circulating level s of tissue Factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies [J]. LuPus,2005, 14(2):129-36.
[36]Holers VM, Girardi G, Mo L, et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss [J]. Exp Med,2002, 195(2):200-201.
[37]Kaplanski G, Cacoub P, Farnarier C, et al. Increased soluble vaseular cell adhesion moleeule 1 concentrations in patients with Primary or systemic lupus erythematosus-related antiphospholipid syndrome:correlations with these verity of thrombosis [J].Arthritis Rheum,2000,43(1):55-64.
[38]Zhang J, MeCrae KR. Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2 glycoproteinl antibodies [J]. Blood,2005, 105(5):1964-1969.
[39]Romay Z, Montiel MG, Shilagard T, et al. Annexin A2 is involved in antiphospholipid antibody-mediated Pathogenic effeets in vitro and invivo [J]. Blood,2009,114(14):3074-83.
[40]Zhou H, Ling S, Yu Y, et al. Involvement of annexin A2 in anti-β2GPI/β2GPI-induced tissue factor expression on monocytes [J]. Cell Res,2007,17(8): 737-739.
[41]Zhou H, Wang H, Li N, et al. Annexin A2 mediates anti-beta2GPI/beta2GPI induced tissue factor expression on monocytes [J]. Int J Mol Med,2009,24(4): 557-562.
[42]Vega-Ostertag AM, Pierangeli SS. Intracellular events in platelet activation induced by antiphospholipid antibodies in the Presence of low doses of thrombin [J]. Arthritis Rheum,2004,50(9):2911-9.
[43]Alard JE, Gaillard F, Daridon C, et al. TLR2 is one of the endothelial receptors for beta 2-glycoprotein I [J]. J Immunol,2010,185(3):1550-1557.
[44]Xu G, Wen H, Zhou H, et al. Involvement of IRAKs and TRAFs in anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells [J]. Thromb Haemost,2011,106(6):1158-1169.
[45]Zhou H, Chen D, Xie H, et al. Activation of MAPKs in the anti-β2GPI/β2GPI-induced tissue factor expression through TLR4/IRAKs pathway in THP-1 cells [J]. Thromb Res,2012,130(4):e229-35.
[46]Xie H, Zhou H, Wang H, et al. Anti-β (2) GPI/β (2) GPI induced TF and TNF-a expression in monocytes involving both TLR4/MyD88 and TLR4/TRIF signaling pathways [J]. Mol Immunol,2013,53(3):246-54.
[47]Green L, Safa O, Machin SJ, et al. Development and application of an automated chromogenic thrombin generation assay that is sensitive to defects in the protein C pathway [J]. Thromb Res,2012,130(5):780-4.
[48]Ames PR, Tommasino C, Iamiaccone L, et al. Coagnlation activation and fibrinolytic imbalance in subjects with idio Pathicantiphospholipid antibodies- a crucial role for acquired free Protein S deficieney [J]. Thromb Haemost,1996, 76(2):190-4.
[49]Hoppensteadt DA, Walenga JM. The relationship between the antiphospholipid syndrome and heparin-induced thrombocytopenia [J]. Hematol Oncol Clin N Am,2008,22(1):1-18.
[50]Lutters BC, Derksen RH, Tekelenburg WL, et al. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2 [J]. J Biol Chem,2003,278(36):33831-33838.
[51]Brandt KJ, Kruithof EK, de Moerloose P. Receptors involved in cell activation by antiphospholipid antibodies [J]. Thromb Res,2013,132(4):408-13.
[52]Hartmut W. Tracing the molecular pathogenesis of antiphospholipid syndrome [J]. J Clin Invest,2008,118(10):3276-3278.
[53]Ohtomo Y, Nagaoka R, Watnabe H, et al. Nonlupus nephropathy associated wth antiphospholipid antibodies [J]. Pediatr Nephrol,2000,15(3):136-138.
[54]Iedermann FJ, Lederer W, Mayr AJ, et al. Prospect iobservational study of antiphopholipid antibody in acute lung in jury and acute respiratory distress syndrome comparison with catastrophic antiphospholipid syndrome [J]. Lupus, 2003,12(6):462-467.
[55]Korkmaz S, Uslu AU, Sahin S, et al. Is there a link between mean platelet volume and thrombotic events in antiphospholipid syndrome? [J]. Platelets,2013,23(8) [Epub ahead of print].
[56]Aung W, Murata Y, IshidaR, et al. Comparison of lung perfusion scintigraphic findings in pulmonary thromoembolism in systemic lupus erythem atosus, SLE plus antiphosphoslipid syndrome, and primary antiphosphoslipid syndrome [J]. NuclMed Commun,2000,21(3):299-304.
[57]Nochy D, Daugas E, Droz D, et al. The intrarenal vascular lesion Associated with primary antiphospholipid syndrome [J]. J Am Soc Nephrol 1999, 10(5):507-518.
[58]Wilson WA, Gharavi AE, Koike T, et al. International consensusstatement on preliminary classification criteria for definite antiphospholipid syndrome:report of an international work shop [J]. Arthritis Rheum,1999,42(7):1309-1311.
[59]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome(APS) [J]. Thromb Haemost,2006,4 (2):295-306.
[60]张杰,赖翔,李晓岚.抗磷脂抗体综合症中医治疗探讨[J].云南中医中药杂志,2011,32(2)：85-86.
[61]Trappe R, Loew A, Thuss-Patience P, et al. Successful treatment of thrombocytopenia in primary antiphospholipid antibody syndrome with the anti-CD20 antibody rituximab-monitoring of antiphospholipid and anti-GP antibodies:a case report [J]. Ann Hematol,2006,85(2):134-5.
[62]Sciascia S, Naretto C, Rossi D, et al. Treatment-induce downregulation of antiphospholipid antibodies:effect of rituximab alone on clinical and laboratory features of antiphospholipid syndrome [J]. Lupus,2011,20(10):1106-8.
[63]Espinosa G, Berman H, Cervera R. Management of refractory cases of catastrophic antiphospholipid syndrome [J]. Autoimmun Rev,2011, 10(11):664-668.
[64]Torres-Aguilar H, Blank M, Kivity S, et al. Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI [J]. Ann Rheum Dis,2012,71(1):120-8.
[65]Yoon KH. Sufficient evidence to consider hydroxychloroquine as an adjunct therapy in antiphospholipid antibody (Hughes') syndrome [J]. J Rheumatol 2002, 29(7):1574-5.
[66]Montiel-Manzano G, Romay-Penabad Z, Papalardo de Martinez E, et al. In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties ofantiphospholipid antibodies [J]. Ann N Y Acad Sci,2007,1108(7):540-53.
[67]Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients [J]. Curr Rheumatol Rep,2011,13(1):77-80.
[68]Iglesias Jimenez E, Camacho-Lovillo M, Falcon-Neyra D, et al. Infant with probable catastrophic antiphospholipid syndrome successfully managed with rituximab [J].2010,125(6):e1523-1528.
[69]Corbacioglu S, Cesaro S, Faraci M, et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation:an open-label, phase 3, randomised controlledtrial [J]. Lancet,2012, 379(9823):1301-9.
[70]Meroni PL, Raschi E, Testoni C,et al. Innate immunity in the antiphospholipid syndrome:role of toll-like receptors in endothelial cell activation by antiphospholipid antibodies [J]. Autoimmun Rev,2004,3(7-8):510-5.
[71]Holy EW, Stampfli SF, Akhmedov A, et al. Laminin receptor activation inhibits endothelial tissue factor expression [J]. Mol Cell Cardio,2010,48(6): 1138-1145.
[72]Shin HY, Kim SH, Jeong HJ, et al. Epigallocatechin-3-gallateinhibits secretion of TNF-α, IL-6 and IL-8 through the attenuation of ERK and NF-κB in HMC-1 cells [J]. Int Arch Allergy Immunol,2007,142(4):335-344.
[73]Lopez-Pedrera C, Buendia P, Cuadrado MJ, et al. Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-κB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-1/ERK pathway [J]. Arthritis Rheum,2006,54(1):301-311.
[74]Hamid C, Norgate K, D'Cruz DP, et al. Anti-β2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome [J]. Ann Rheum Dis,2007,66(8):1000-1007.
[75]Zhou H, Yan Y, Xu G, et al. Toll-like receptor (TLR)-4 mediates anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells [J]. Clin Exp Immunol,2011,163(2):189-198.
[76]Porath D, Riegger C, Drewe J, et al. Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines [J]. Pharmacol Exp Ther,2005,315(3):1172-1180.
[77]Pajonk F, Riedisser A, Henke M, et al. The effects of tea extracts on proinflammatory signaling [J]. BMC Med,2006,4(1):28.
[78]Xia LF, Zhou H, Hu LC, et al. Both NF-κB and c-Jun/AP-1 involved in anti-β2GPI/β2GPI-induced tissue factor expression in monocytes [J]. Thromb Haemost,2013,109(4):569-768.
[79]Lee HS, Chauhan SK, Okanobo A, et al. Topical EGCG for Treatment of Dry Eye Disease [J]. Invest Ophthalmol,2010,51(4):1465-72..
[80]Porath D, Riegger C, Drewe J, et al. Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines [J]. Pharmacol Exp Ther,2005,315(3):1172-1180.
[81]Pajonk F, Riedisser A, Henke M, et al. The effects of tea extracts on proinflammatory signaling [J]. BMC Med,2006,4(10):28.
[82]Lin YL, L JK. (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB [J]. Mol Pharmacol,1997,52(3): 465-472.
[83]Ahn SC, Kim GY, Kim JH, et al. Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB [J]. Biochem Biophys Res Commun,2004,313(1):148-155,
[84]Youn HS, Lee JY, Saitoh SI, et al. Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem [J]. Pharmacol,2006,72(7): 850-859,
[85]Liu JM, Xiong YQ. Effect of pravastatin on transportation of scutellarin in mouse liver and its mechanism [J]. Acta Pharm Sin,2011,46 (3):269-273.
[86]Zhang S, Doudican N, Quay E, et al. Fluvastatin Enhances Sorafenib Cytotoxicity in Melanoma Cells via Modulation of AKT and JNK Signaling Pathways [J]. Anticancer Research,2011,31(10):3259-3265.
[87]Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes [J]. N Engl J Med,2007, 356(24):2457-2471.
[88]Loppnow H, Buerke M, Schlitt A, et al. Anti-inflammatory effect of statins in an atherosclerosis-related coculture model [J]. FASEB,2011,25(4):638-643.
[89]Haramaki N, Ikeda H, Takenaka K, et al. Fluvastatin Alters Platelet Aggregability in Patients with Hypercholesterolemia [J]. Arteriosclerosis Thrombosis and Vascular Biology,2007,27(6):1471-1477.
[90]Holschermann H, Schuster D, Parviz B et al. Statins prevent NF-kappaB transactivation independently of the IKK-pathway in human endothelial cells [J]. Atherosclerosis,2006,185(2):240-5.
[91]Erkan D, Pierangeli SS. Could statins be a new therapeutic option for antiphospholipid syndrome patients? [J]. Expert Rev Hematol,2013, 6(2):115-7.
[2]陈晓微,申艳,杨程德等.抗磷脂综合征174例临床特点及与欧洲数据的比较分析[J].中华风湿病学杂志,2010,14(6)：394-397.
[3]Avalos I, Tsokos GC. The role of complement in the antiphospholipid syndrome-associated pathology [J]. Clin Rev Allergy Immunol,2009,36 (1):141-144.
[4]Hedge VA, Vivas Y, Shah H, et al. Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome-a case series [J]. Heart Lung Circ,2007, 16(6):423-437.
[5]Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies [J]. Arthritis Rheum,2012, 64(7):2311-2318.
[6]McNeil HP, Simpson RJ, Chesterman CN, et al. Antiphospholipid antibodies are directed against a complex antigen that induces a lipid-binding inhibitor of coagulant:β2-glycoprotein Ⅰ [J]. Proc Natl Acid,1990,87(7):4120-4124.
[7]Willis R, Pierangeli SS. Anti-β2-glycoprotein I antibodies [J]. Ann N Y Acad Sci,2013,1285(5):44-58.
[8]Nojima J, Kuratsune H, Suehisa E, et al. Association between the prevalence of antibodies to beta 2-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications [J]. Clin Chem,2001,47(7):1008-1015.
[9]Zhou H, Wolberg AS, Roubey RA. Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep [J]. Blood,2004,104(8):2353-2358.
[10]Rahgozar S. Revisiting Beta 2 glycoprotein I, the major autoantigen in the antiphospholipid syndrome [J]. Iran J Immunol,2012,9(2):73-85.
[11]Levine JS, Branch DW, Rauch J.The antiphospholipid syndrome [J]. N Engl Med,2002,346(10):752-763.
[12]Singh NK, Behera DR, Agrawal, A et al. Hospital based prospective longitudinal clinical and immunologic study of 179 patients of primary anti-phospholipid syndrome [J]. Int J Rheum Dis,2013,16(5):547-547.
[13]Blank M, Krause I, Fridkin M, et al. Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome [J]. Clin Invest,2002,109(6):797-804.
[14]Sene D, Piette JC, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and infections [J]. Autoimmun Rev,2008,7(4):272-277.
[15]Cabiedes J, Cabral AR. Anti-beta2-glycoprotein-Ⅰ antibodies in sc Fv format [J]. Autoimmun Rev,2005,4(5):289-295.
[16]GiannakoPoulos B, Passam F, Rahgozar S, et al. Current concepts on the pathogenesis of the antiphospholipid syndrome [J]. Blood,2007, 109(2):422-430.
[17]Matsuura E, Lopez LR, Shoenfeld Y, et al. β2-glycoprotein I and oxidative inflammation in early atherogenesis:a progression from innate to adaptive immunity? [J]. Autoimmun Rev,2012,12(2):241-249.
[18]Stojanovich L, Kontic M, Smiljanic D, et al. Association between non-thrombotic neurological and cardiac manifestations in patients with antiphospholipid syndrome [J]. Clin Exp Rheumatol,2013,31(5):756-60.
[19]Raby A, Moffat K, Crowther M. Anticardiolipin antibody and anti-beta 2 glycoprotein I antibody assays [J]. Methods Mol Biol,2013,992:387-405..
[20]杨朝东,史伟雄,夏健,等.β2-糖蛋白Ⅰ与脑卒中关系的研究[J].中华内科杂志,2003,42(3)：192-193.
[21]Groot PG, Meijers JC. β(2)-Glycoprotein Ⅰ:evolution, structure and function [J]. Thromb Haemost,2011,9(7):1275-1284.
[22]Roubey RA. Immunology of the antiphospholipid syndrome:antibodies, antigens, and antiimmune response [J].Thromb Haemost,1999,82(2):656-661.
[23]MeNeeley PA, Dlott JS, Furie RA, et al. beta2-glycoprotein-dependent anficardiolipin antibodies pref-erentially bind the amino terminal domain of beta 2-glycoproteinl [J]. Thromb Haemost,2001,86(2):590-595.
[24]Blank M, Shoenfeld Y, Cabilly S, et al. Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides [J]. ProcNatl Acad Sci USA,1999,96(9):5164-5168.
[25]Yang CD, Chen SL, Shen N, et al. Deteetion of antirecombint beta 2-glycoprotein fifth-domain antibodies in sera from patients with systemic lupus erythematosus [J]. Rheumatol Int,1998,18(1):5-10.
[26]Basde LH, Derksen RH, deGroot PG. Beta2-glycoprotein 1, the Playmaker of the antiphospholipid syndrome [J].Clin Immunol,2004,112(2):161-168.
[27]Sciascia S, Sanna G, Murru V, et al. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome, a systematic review [J]. Thromb Haemost,2013,111 (2):epub.
[28]Ghirardello A, Bizzaro N, Zampieri S, et al. Biological and clinical relevance of anti-prothrombin antibodies [J]. Ann NY Acad Sci,2007,1109(4):503-510.
[29]Jaskowski TD, Wilson AR, Hill HR, et al. Autoantibodies against phosphatidylserine, prothrombin and phosphatidylserine-prothrombin complex:identical or distinct diagnostic tools for antiphospholipid syndrome [J]. Clin Chim Aeta,2009,4(10):19-24.
[30]Pengo V, Denas G, Bison E, et al. On behalf of participating centers of Italian Federation of Thrombosis Centers (FCSA). Prevalence and siginificance of anti-prothrombin (aPT) antibodies in patients with lupus anticoagulant (LA) [J]. Thromb Res,2010,126(2):150-3.
[31]Sakai Y, Atsumi T, Ieko M, et al. The effects of phosphatidylserine-dependent antiprothrombin antibody on thrombingen-eration [J]. Arthritis Rheum,2009,60(8):2457-67.
[32]Rand JH, Wu XX, Andree HA, et al. Pregnancy loss in the antiphospholipid-antibody syndrome -a possible thromobogenic mechanism [J]. N Engl J Med,1997,337 (3):154-160.
[33]Singh NK, Yadav DP, Gupta A, et al. Role of anti-annexin A5 in pathogenesis of hypercoagulable state in patients with antiphospholipid syndrome [J]. Int J Rheum Dis,2013,16(3):325-30.
[34]Pierangeli SS, Espinola RG, Liu X, et al. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1 Vascular cell adhesion molecule-1, and p-selectin [J]. Cire Res,2001, 88(2):245-50.
[35]Forastiero RR, Martinuzzo ME, delarranaga GF. Circulating level s of tissue Factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies [J]. LuPus,2005, 14(2):129-36.
[36]Holers VM, Girardi G, Mo L, et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss [J]. Exp Med,2002, 195(2):200-201.
[37]Kaplanski G, Cacoub P, Farnarier C, et al. Increased soluble vaseular cell adhesion moleeule 1 concentrations in patients with Primary or systemic lupus erythematosus-related antiphospholipid syndrome:correlations with these verity of thrombosis [J].Arthritis Rheum,2000,43(1):55-64.
[38]Zhang J, MeCrae KR. Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2 glycoproteinl antibodies [J]. Blood,2005, 105(5):1964-1969.
[39]Romay Z, Montiel MG, Shilagard T, et al. Annexin A2 is involved in antiphospholipid antibody-mediated Pathogenic effeets in vitro and invivo [J]. Blood,2009,114(14):3074-83.
[40]Zhou H, Ling S, Yu Y, et al. Involvement of annexin A2 in anti-β2GPI/β2GPI-induced tissue factor expression on monocytes [J]. Cell Res,2007,17(8): 737-739.
[41]Zhou H, Wang H, Li N, et al. Annexin A2 mediates anti-beta2GPI/beta2GPI induced tissue factor expression on monocytes [J]. Int J Mol Med,2009,24(4): 557-562.
[42]Vega-Ostertag AM, Pierangeli SS. Intracellular events in platelet activation induced by antiphospholipid antibodies in the Presence of low doses of thrombin [J]. Arthritis Rheum,2004,50(9):2911-9.
[43]Alard JE, Gaillard F, Daridon C, et al. TLR2 is one of the endothelial receptors for beta 2-glycoprotein I [J]. J Immunol,2010,185(3):1550-1557.
[44]Xu G, Wen H, Zhou H, et al. Involvement of IRAKs and TRAFs in anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells [J]. Thromb Haemost,2011,106(6):1158-1169.
[45]Zhou H, Chen D, Xie H, et al. Activation of MAPKs in the anti-β2GPI/β2GPI-induced tissue factor expression through TLR4/IRAKs pathway in THP-1 cells [J]. Thromb Res,2012,130(4):e229-35.
[46]Xie H, Zhou H, Wang H, et al. Anti-β (2) GPI/β (2) GPI induced TF and TNF-a expression in monocytes involving both TLR4/MyD88 and TLR4/TRIF signaling pathways [J]. Mol Immunol,2013,53(3):246-54.
[47]Green L, Safa O, Machin SJ, et al. Development and application of an automated chromogenic thrombin generation assay that is sensitive to defects in the protein C pathway [J]. Thromb Res,2012,130(5):780-4.
[48]Ames PR, Tommasino C, Iamiaccone L, et al. Coagnlation activation and fibrinolytic imbalance in subjects with idio Pathicantiphospholipid antibodies- a crucial role for acquired free Protein S deficieney [J]. Thromb Haemost,1996, 76(2):190-4.
[49]Hoppensteadt DA, Walenga JM. The relationship between the antiphospholipid syndrome and heparin-induced thrombocytopenia [J]. Hematol Oncol Clin N Am,2008,22(1):1-18.
[50]Lutters BC, Derksen RH, Tekelenburg WL, et al. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2 [J]. J Biol Chem,2003,278(36):33831-33838.
[51]Brandt KJ, Kruithof EK, de Moerloose P. Receptors involved in cell activation by antiphospholipid antibodies [J]. Thromb Res,2013,132(4):408-13.
[52]Hartmut W. Tracing the molecular pathogenesis of antiphospholipid syndrome [J]. J Clin Invest,2008,118(10):3276-3278.
[53]Ohtomo Y, Nagaoka R, Watnabe H, et al. Nonlupus nephropathy associated wth antiphospholipid antibodies [J]. Pediatr Nephrol,2000,15(3):136-138.
[54]Iedermann FJ, Lederer W, Mayr AJ, et al. Prospect iobservational study of antiphopholipid antibody in acute lung in jury and acute respiratory distress syndrome comparison with catastrophic antiphospholipid syndrome [J]. Lupus, 2003,12(6):462-467.
[55]Korkmaz S, Uslu AU, Sahin S, et al. Is there a link between mean platelet volume and thrombotic events in antiphospholipid syndrome? [J]. Platelets,2013,23(8) [Epub ahead of print].
[56]Aung W, Murata Y, IshidaR, et al. Comparison of lung perfusion scintigraphic findings in pulmonary thromoembolism in systemic lupus erythem atosus, SLE plus antiphosphoslipid syndrome, and primary antiphosphoslipid syndrome [J]. NuclMed Commun,2000,21(3):299-304.
[57]Nochy D, Daugas E, Droz D, et al. The intrarenal vascular lesion Associated with primary antiphospholipid syndrome [J]. J Am Soc Nephrol 1999, 10(5):507-518.
[58]Wilson WA, Gharavi AE, Koike T, et al. International consensusstatement on preliminary classification criteria for definite antiphospholipid syndrome:report of an international work shop [J]. Arthritis Rheum,1999,42(7):1309-1311.
[59]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome(APS) [J]. Thromb Haemost,2006,4 (2):295-306.
[60]张杰,赖翔,李晓岚.抗磷脂抗体综合症中医治疗探讨[J].云南中医中药杂志,2011,32(2)：85-86.
[61]Trappe R, Loew A, Thuss-Patience P, et al. Successful treatment of thrombocytopenia in primary antiphospholipid antibody syndrome with the anti-CD20 antibody rituximab-monitoring of antiphospholipid and anti-GP antibodies:a case report [J]. Ann Hematol,2006,85(2):134-5.
[62]Sciascia S, Naretto C, Rossi D, et al. Treatment-induce downregulation of antiphospholipid antibodies:effect of rituximab alone on clinical and laboratory features of antiphospholipid syndrome [J]. Lupus,2011,20(10):1106-8.
[63]Espinosa G, Berman H, Cervera R. Management of refractory cases of catastrophic antiphospholipid syndrome [J]. Autoimmun Rev,2011, 10(11):664-668.
[64]Torres-Aguilar H, Blank M, Kivity S, et al. Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI [J]. Ann Rheum Dis,2012,71(1):120-8.
[65]Yoon KH. Sufficient evidence to consider hydroxychloroquine as an adjunct therapy in antiphospholipid antibody (Hughes') syndrome [J]. J Rheumatol 2002, 29(7):1574-5.
[66]Montiel-Manzano G, Romay-Penabad Z, Papalardo de Martinez E, et al. In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties ofantiphospholipid antibodies [J]. Ann N Y Acad Sci,2007,1108(7):540-53.
[67]Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients [J]. Curr Rheumatol Rep,2011,13(1):77-80.
[68]Iglesias Jimenez E, Camacho-Lovillo M, Falcon-Neyra D, et al. Infant with probable catastrophic antiphospholipid syndrome successfully managed with rituximab [J].2010,125(6):e1523-1528.
[69]Corbacioglu S, Cesaro S, Faraci M, et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation:an open-label, phase 3, randomised controlledtrial [J]. Lancet,2012, 379(9823):1301-9.
[70]Meroni PL, Raschi E, Testoni C,et al. Innate immunity in the antiphospholipid syndrome:role of toll-like receptors in endothelial cell activation by antiphospholipid antibodies [J]. Autoimmun Rev,2004,3(7-8):510-5.
[71]Holy EW, Stampfli SF, Akhmedov A, et al. Laminin receptor activation inhibits endothelial tissue factor expression [J]. Mol Cell Cardio,2010,48(6): 1138-1145.
[72]Shin HY, Kim SH, Jeong HJ, et al. Epigallocatechin-3-gallateinhibits secretion of TNF-α, IL-6 and IL-8 through the attenuation of ERK and NF-κB in HMC-1 cells [J]. Int Arch Allergy Immunol,2007,142(4):335-344.
[73]Lopez-Pedrera C, Buendia P, Cuadrado MJ, et al. Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-κB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-1/ERK pathway [J]. Arthritis Rheum,2006,54(1):301-311.
[74]Hamid C, Norgate K, D'Cruz DP, et al. Anti-β2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome [J]. Ann Rheum Dis,2007,66(8):1000-1007.
[75]Zhou H, Yan Y, Xu G, et al. Toll-like receptor (TLR)-4 mediates anti-β2GPI/β2GPI-induced tissue factor expression in THP-1 cells [J]. Clin Exp Immunol,2011,163(2):189-198.
[76]Porath D, Riegger C, Drewe J, et al. Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines [J]. Pharmacol Exp Ther,2005,315(3):1172-1180.
[77]Pajonk F, Riedisser A, Henke M, et al. The effects of tea extracts on proinflammatory signaling [J]. BMC Med,2006,4(1):28.
[78]Xia LF, Zhou H, Hu LC, et al. Both NF-κB and c-Jun/AP-1 involved in anti-β2GPI/β2GPI-induced tissue factor expression in monocytes [J]. Thromb Haemost,2013,109(4):569-768.
[79]Lee HS, Chauhan SK, Okanobo A, et al. Topical EGCG for Treatment of Dry Eye Disease [J]. Invest Ophthalmol,2010,51(4):1465-72..
[80]Porath D, Riegger C, Drewe J, et al. Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines [J]. Pharmacol Exp Ther,2005,315(3):1172-1180.
[81]Pajonk F, Riedisser A, Henke M, et al. The effects of tea extracts on proinflammatory signaling [J]. BMC Med,2006,4(10):28.
[82]Lin YL, L JK. (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB [J]. Mol Pharmacol,1997,52(3): 465-472.
[83]Ahn SC, Kim GY, Kim JH, et al. Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB [J]. Biochem Biophys Res Commun,2004,313(1):148-155,
[84]Youn HS, Lee JY, Saitoh SI, et al. Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem [J]. Pharmacol,2006,72(7): 850-859,
[85]Liu JM, Xiong YQ. Effect of pravastatin on transportation of scutellarin in mouse liver and its mechanism [J]. Acta Pharm Sin,2011,46 (3):269-273.
[86]Zhang S, Doudican N, Quay E, et al. Fluvastatin Enhances Sorafenib Cytotoxicity in Melanoma Cells via Modulation of AKT and JNK Signaling Pathways [J]. Anticancer Research,2011,31(10):3259-3265.
[87]Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes [J]. N Engl J Med,2007, 356(24):2457-2471.
[88]Loppnow H, Buerke M, Schlitt A, et al. Anti-inflammatory effect of statins in an atherosclerosis-related coculture model [J]. FASEB,2011,25(4):638-643.
[89]Haramaki N, Ikeda H, Takenaka K, et al. Fluvastatin Alters Platelet Aggregability in Patients with Hypercholesterolemia [J]. Arteriosclerosis Thrombosis and Vascular Biology,2007,27(6):1471-1477.
[90]Holschermann H, Schuster D, Parviz B et al. Statins prevent NF-kappaB transactivation independently of the IKK-pathway in human endothelial cells [J]. Atherosclerosis,2006,185(2):240-5.
[91]Erkan D, Pierangeli SS. Could statins be a new therapeutic option for antiphospholipid syndrome patients? [J]. Expert Rev Hematol,2013, 6(2):115-7.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |