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同型半胱氨酸对内皮细胞CD40 表达的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2004年第5期
页码:
431-434
栏目:
基础研究
出版日期:
2004-09-01

文章信息/Info

Title:
Effect of homocysteine on CD40 expression in endothelial cells
作者:
蒋　晖;  李　锦;  毛建斌;  陈　茂;  范忠才;  黄德嘉
四川大学华西医院心内科, 四川成都610041
Author(s):
JIANG Hui ;  LI Jin ;  MAO Jian-bin ;  CHEN Mao ;  FAN Zhong-cai ;  HUANG De-jia
Department of Cardiology , West China Hospital , Sichuan University , Chengdu ,Sichuan 610041
关键词:
同型半胱氨酸; 动脉粥样硬化; 炎症; CD40 ; 内皮细胞
Keywords:
homocysteine ;  atherosclerosis ;  inflammation ;  CD40 ;  endothelial cell
分类号:
Q26
DOI:
-
文献标识码:
A
摘要:
目的:研究同型半胱氨酸(Hcy) 对内皮细胞CD40 表达的影响。方法:体外培养ECV304 细胞,然后分组实 验: ①对照组; ②20μmol/ L Hcy 组; ③50μmol/ L Hcy 组; ④100μmol/ L Hcy 组; ⑤吡咯二硫氨基甲酸酯(PDTC) 预处 理组; ⑥普伐他汀预处理组。Hcy 的作用时间均为24 h。运用流式细胞仪检测细胞CD40 的表达;用分光光度计测 定细胞培养上清液中H2O2 的含量。结果: ①Hcy 呈浓度依赖关系(0～100μmol/ L) 增加内皮细胞CD40 的表达。② 在Hcy 作用下,培养上清液中H2O2 的含量较对照组显著增加( P < 0. 01) 。③ PDTC 和普伐他汀预处理组与100 μmol/ L Hcy 组比较,CD40 表达及H2O2 水平均降低。④内皮细胞CD40 的表达与上清液中H2O2 含量呈正相关( r = 0. 702 , P < 0. 01) 。结论:Hcy 能促进内皮细胞CD40 的表达,其中有氧化应激作用的参与。CD40 高表达所引起的炎 症激活可能是Hcy 致动脉粥样硬化的重要机制之一。
Abstract:
AIM: To investigate the effect of homocysteine (Hcy) on the expression of CD40 in cultured endothelial cells (ECs) . METHODS: ECV304 cells were incubated in vitro , then exposed to Hcy at the concentrations of 0、20 、50 、100 μmol/ L for 24h , of which , some cells were pretreated with pyrrolidinedithiocarbamate (PDTC) or pravastatin for 24h before the exposure to 100μmol/ L Hcy. Flow cytometry was performed to measure the expression of CD40. Spectrophotometer was used to detect the production of H2O2 in the culture medium. RESULTS :Flow cytometry showed that Hcy significantly increased CD40 expression in a concentration-dependent manner. Spectrophotometry showed that Hcy at concentrations of 20 , 50 and 100μmol/ L resulted in a 1. 71 ±0. 042fold , a 1. 76 ±0. 052fold and a 1. 99 ±0. 052fold increase respectively in the production of H2O2 , as compared with the control group. In the presence of PDTC or pravastatin , both the expression of CD40 and production of H2O2 declined , compared with the 100μmol/ L Hcy group. There was a positive correlation between CD40 expression and H2O2 production ( r = 0. 702 , P < 0. 01) . CONCLUSION:Hcy can increase CD40 expression in ECs , and oxidative stress plays a role during the process. Inflammation activated by a high CD40 expression may be an important atherogenic mechanism of Hcy.

参考文献/References

[1 ] Hofmann MA , Lalla E , Lu Y, et al . Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model [J ] . J Clin Invest , 2001 , 107 : 675 - 683.

[2 ] Katherine AH. Homocysteine : a sulphurous fire [ J ] . J Clin Invest ,2001 , 107 : 663 - 664.

[3 ] Phipps RP. Atherosclerosis : The emerging role of inflammation and the CD40 - CD40 ligand system[J ] . Proc Natl Acad Sci USA , 2000 , 97(13) : 6930 - 6932.

[4 ] Lutgens E , Cleutjens KBJM, Heeneman S , et al . Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype [J ] . Proc Natl Acad Sci USA , 2000 , 97 (13) : 7464 7469.

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[7 ] 闫韵洪,张利华. 同型半胱氨酸与冠状动脉粥样硬化的相关性[J ] . 心脏杂志,2002 ,14(4) :303 - 304.

[8 ] 唐梦熊,黄文增,张步延,等. 血浆同型半胱氨酸对冠心病患者血管内皮功能的影响[J ] . 心脏杂志,2002 ,14(4) :305 - 309.

[9 ] Wagner AH , Gebauer M, Güldenzoph B , et al . 3-hydroxy-3 -methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells[J ] . Arterioscler Thromb Vasc Biol , 2002 , 22 :1784 - 1789.

备注/Memo

备注/Memo:
收稿日期：2004-3-13
更新日期/Last Update: 2004-09-01