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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (5): 1-4.doi: 10.6040/j.issn.1671-7554.2.2015.001

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他汀对动脉粥样硬化的免疫调节及其在临床应用中的思考

段瑞生   

  1. 山东大学附属千佛山医院神经内科, 山东 济南 250014
  • 收稿日期:2015-02-24 修回日期:2015-04-07 出版日期:2015-05-10 发布日期:2015-05-10
  • 通讯作者: 段瑞生。E-mail: ruisheng_duan@yahoo.com E-mail:ruisheng_duan@yahoo.com
  • 基金资助:
    国家自然科学基金(81171128,81471222);山东省泰山学者建设工程专项经费(ts20130914)

Immune-regulation of statins in atherosclerosis and opinions on its clinical applications

DUAN Ruisheng   

  1. Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
  • Received:2015-02-24 Revised:2015-04-07 Online:2015-05-10 Published:2015-05-10

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摘要： 动脉粥样硬化的本质是免疫反应发生的炎症过程,氧化的低密度脂蛋白等抗原在动脉内膜下触发了固有免疫(非特异性免疫)和适应性免疫(特异性免疫)反应。斑块中的免疫炎性细胞包括巨噬细胞、CD4+和CD8+T细胞、B细胞、树突状细胞(DCs)、调节性T细胞(Treg)、NK细胞、嗜中性粒细胞和肥大细胞等。目前发现他汀类药物有明确的抗炎和免疫抑制作用,临床上已用于部分自身免疫性疾病的辅助治疗。他汀在动脉粥样硬化中的疗效源于其降脂和抗炎的双重作用。超敏C反应蛋白(hsCRP)是动脉粥样硬化的炎性生物学标志之一,升高的hsCRP与低密度脂蛋白都是心脑血管事件发生的危险因素,在预测血管事件发生上可能具有同等重要的作用。在动脉粥样硬化的防治中,要对低密度脂蛋白和超敏C反应蛋白进行双重控制。

关键词: 他汀类药物, 免疫反应, 超敏C反应蛋白, 动脉粥样硬化

Abstract: It has been demonstrated that the pathogenesis of atherosclerosis is characteristic of inflammation and immune responses, which includes innate and adaptive immune responses to oxidative lipoprotein. The immune cells in the atherosclerotic plaque include macrophages, CD4+ and CD8+ T cells, B cells, dendritic cells, regulatory T cells, NK cells, neurophils and mast cells. Statins have anti-inflammatory and immune suppressive roles and have been applied in the treatment of autoimmune diseases. The statin benefit observed in the atherosclerosis is due to both lipid-lowing and anti-inflammatory effects. Hypersensitive C-reactive protein (hsCRP), an inflammatory marker of atherosclerosis, and low-density lipoprotein cholesterol (LDL-C) are equally strong predictors of cardiovascular risk. Both LDL-C and hsCRP should be monitored in the prevention and treatment of atherosclerosis.

Key words: Immune responses, Atherosclerosis, Statins, Hypersensitive C-reactive protein

中图分类号: 

  • R543.5
[1] Witztum JL, Lichtman AH. The influence of innate and adaptive immune responses on atherosclerosis[J]. Annu Rev Pathol, 2014(9):73-102.
[2] Hansson GK, Hermansson A. The immune system in atherosclerosis[J]. Nat Immunol, 2011, 12(3):204-212.
[3] Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options[J]. Nat Med, 2011, 17(11):1410-1422.
[4] Sigal LH. Basic science for the clinician 44: atherosclerosis: an immunologically mediated (autoimmune?) disease[J]. J Clin Rheumatol, 2007, 13(3):160-168.
[5] Sakakura K, Nakano M, Otsuka F, et al. Pathophysiology of atherosclerosis plaque progression[J]. Heart Lung Circ, 2013, 22(6):399-411.
[6] Bu DX, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins[J]. Curr Opin Lipidol, 2011, 22(3):165-170.
[7] Chalubinski M, Broncel M. Influence of statins on effector and regulatory immune mechanisms and their potential clinical relevance in treating autoimmune disorders[J]. Med Sci Monit, 2010, 16(11):RA245-251.
[8] Weber MS, Zamvil SS. Statins and demyelination[J]. Curr Top Microbiol Immunol, 2008, 318:313-324.
[9] Li XL, Dou YC, Liu Y, et al. Atorvastatin ameliorates experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells[J]. Cell Immunol, 2011, 271(2):455-461.
[10] Forero-Pena DA, Gutierrez FR. Statins as modulators of regulatory T-cell biology[J]. Mediators Inflamm, 2013, 2013:167086. doi: 10.1155/2013/167086.
[11] Li XL, Liu Y, Cao LL, et al. Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines[J]. Mol Cell Neurosci, 2013, 56:85-95. doi: 10.1016/j.mcn.2013.03.005.
[12] Xu H, Li XL, Yue LT, et al. Therapeutic potential of atorvastatin-modified dendritic cells in experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells and NKR-P1(+) cells[J]. J Neuroimmunol, 2014, 269(1-2):28-37.
[13] Khattri S, Zandman-Goddard G. Statins and autoimmunity[J]. Immunol Res, 2013, 56(2-3):348-357.
[14] Wang J, Xiao Y, Luo M, et al. Statins for multiple sclerosis[J]. Cochrane Database Syst Rev, 2010, 2010(12):CD008386. doi:10.1002/14651858.CD008386.pub2.
[15] Meng X, Zhang K, Li J, et al. Statins induce the accumulation of regulatory T cells in atherosclerotic plaque[J]. Mol Med, 2012(18):598-605. doi: 10.2119/molmed.2011.00471.
[16] Everett BM, Glynn RJ, MacFadyen JG, et al. Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)[J]. Circulation, 2010, 121(1):143-150.
[17] Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein[J]. N Engl J Med, 2008, 359(21):2195-2207.
[18] Ridker PM. Moving beyond JUPITER: will inhibiting inflammation reduce vascular event rates?[J]. Curr Atheroscler Rep, 2013, 15(1):295.
[19] Ridker PM,Silvertown JD. Inflammation, C-reactive protein, and atherothrombosis[J]. J Periodontol, 2008, 79(8 Suppl):1544-1551.
[20] Morrow DA, de Lemos JA, Sabatine MS, et al. Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial[J]. Circulation, 2006, 114(4):281-288.
[21] Ridker PM. Inflammation, C-reactive protein, and cardiovascular disease: moving past the marker versus mediator debate[J]. Circ Res, 2014, 114(4):594-595.
[22] Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adul-2009 recommendations[J]. Can J Cardiol, 2009, 25(10):567-579.
[23] Ridker PM, Kastelein JJ, Genest J, et al. C-reactive protein and cholesterol are equally strong predictors of cardiovascular risk and both are important for quality clinical care[J]. Eur Heart J, 2013, 34(17):1258-1261.
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