中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (53): 10007-10010.doi: 10.3969/j.issn.1673-8225.2011.53.031

• 移植与免疫 transplantation and Immunology • 上一篇    下一篇

鼻饲热休克蛋白65诱导免疫耐受降低动脉粥样硬化的形成及其机制

李海禹，丁艳萍，曾秋棠   

  1. 华中科技大学同济医学院附属协和医院心内科，湖北省武汉市 430022
  • 收稿日期:2011-09-27 修回日期:2011-10-23 出版日期:2011-12-31 发布日期:2011-12-31
  • 通讯作者: 曾秋棠，教授，主任医师，华中科技大学同济医学院附属协和医院心内科，湖北省武汉市 430022 zqtdoctor@sina.com
  • 作者简介:李海禹☆，男，1983年生，河南省郑州市人，汉族，华中科技大学同济医学院在读博士， 主要从事冠心病的临床治疗及基础研究。 lihaiyu156239@sina.com 并列第一作者：丁艳萍☆，女，1965年生，河南省洛阳市人，汉族，2011年华中科技大学同济医学院毕业，博士，副主任医师，主要从事冠心病的临床诊治与研究工作。
  • 基金资助:

    国家自然基金项目一部分(81070237)，课题名称：经鼻诱导Th3细胞活化负向调节动脉粥样硬化机制研究。

Effect of nasal tolerance induction to heat shock protein-65 on atherosclerosis and potential mechanism

Li Hai-yu, Ding Yan-ping, Zeng Qiu-tang   

  1. Department of Cardiology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan  430022, Hubei Province, China
  • Received:2011-09-27 Revised:2011-10-23 Online:2011-12-31 Published:2011-12-31
  • Contact: Zeng Qiu-tang, Professor, Chief physician, Department of Cardiology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China zqtdoctor@sina.com
  • About author:Li Hai-yu☆, Studying for doctorate, Department of Cardiology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China lihaiyu156239@sina.com Ding Yan-ping☆, Doctor, Associate chief physician, Department of Cardiology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China Li Hai-yu and Ding Yan-ping contributed equally to this paper.
  • Supported by:

    the National Natural Science Foundation of China, No. 81070237*

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被引次数

1

摘要：

背景：大量研究表明CD4+CD25+Foxp3+ 调节性T细胞与口服耐受和动脉粥样硬化抑制有关，然而有关经鼻耐受是否也有同样效应的报道较少。
目的：分析热休克蛋白65经鼻诱导免疫耐受对动脉粥样硬化的影响及其机制。
方法：6周龄ApoE基因敲除小鼠经鼻给予热休克蛋白65(实验组)或磷酸盐缓冲液(对照组)，待小鼠16周龄时行冰冻切片测定小鼠主动脉根部粥样硬化斑块面积；流式细胞学检测小鼠体内CD4+CD25+Foxp3+  调节性T细胞水平；ELISA检测转化生长因子β水平。
结果与结论：经鼻给药后8周，实验组小鼠主动脉根部斑块面积较对照组明显减少，下降约32.7%(P < 0.01)；经鼻给药14 d后，实验组小鼠CD4+CD25+Foxp3+ 调节性T细胞较对照组明显增加(P < 0 .01)；经鼻给药第4，14天和8周，实验组转化生长因子β表达显著高于对照组。表明鼻饲热休克蛋白65通过诱导依赖抗炎因子转化生长因子β作用的调节性T细胞的产生建立免疫耐受，进一步抑制动脉粥样硬化形成，推测热休克蛋白65经鼻诱导免疫耐受是口服诱导免疫耐受之外另一种有效的抑制动脉粥样硬化的方法。

关键词: 动脉粥样硬化, 免疫耐受, 热休克蛋白, 调节性T细胞, 鼻饲

Abstract:

BACKGROUND: A body of evidences support that CD4+CD25+Foxp3+ regulatory T cells is associated with oral tolerance induction and inhibition of atherosclerosis, but little is described whether nasal tolerance to antigen likewise induce the regulatory T cell production and antiatherosclerotic benefit.
OBJECTIVE: To investigate the effect of nasal tolerance induction to heat shock protein-65 (HSP65) on atherogenesis and potential mechanism.
METHODS: Six-week-old male ApoE-/- mice were nasally administrated HSP65 or phosphate buffer as control. Cryo-section was used to examine the size of atheromatous plaque area of aortic root in ApoE-/- mice with sixteen-week-old; fluorescence activated cell sorter was used to analyse the production level of CD4+CD25+Foxp3+ regulatory T cells; ELISA was applied to determine the level of cytokines transforming growth factor beta (TGF-β).
RESULTS AND CONCLUSION: Eight weeks after nasal administration, the results of cryo-section showed that HSP65-treated mice had a marked decrease by 32.7% in atheromatous plaque area of aortic root as compared with the control group (P < 0.01). At 14 days after the last nasal treatment, the percentage of CD4+CD25+Foxp3+ regulatory T cells in total CD4+ T cells from treated mice increased significantly as compared with the control group (P < 0.01), at 4,14 days and 8 weeks after the last nasal administration, cytokine TGF-β level from nasal HSP65 mice increased remarkably compared with the control group on the above three points. So, nasal tolerance induction to heat shock protein-65 inhibits atherosclerotic formation by inducing anti-inflammatory cytokine TGF-β-dependent regulatory T cells. It is proposed that nasal tolerance induction to HSP65 may provide an alternative therapeutic method to atherosclerosis.

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