基础医学与临床 ›› 2009, Vol. 29 ›› Issue (1): 19-23.

• 研究论文 • 上一篇    下一篇

硫化氢抑制apoE基因敲除小鼠动脉粥样硬化中ICAM-1的表达

王燕飞 唐朝枢 杜军保   

  1. 北京大学第一医院儿科 北京大学第一医院心血管病研究所 北京大学第一医院儿科
  • 收稿日期:2007-05-24 修回日期:2008-01-23 出版日期:2009-01-25 发布日期:2009-01-25
  • 通讯作者: 杜军保

Hydrogen sulfide inhibits expression of intercellular adhesion molecule-1 in the pathogenesis of atherosclerosis in apoE knockout mice

Yan-fei WANG, Chao-shu TANG, Jun-bao DU   

  1. Department of Pediatrics, Peking University First Hospital Institute of Cardiovascular Research, Peking University First Hospital Department of Pediatrics, Peking University First Hospital
  • Received:2007-05-24 Revised:2008-01-23 Online:2009-01-25 Published:2009-01-25
  • Contact: Jun-bao DU

摘要: 目的 探讨硫化氢(H2S)对apoE基因敲除小鼠(apoE-/-小鼠)动脉粥样硬化中细胞间黏附分子-1 (ICAM-1)的调节作用。方法 6周龄雄性C57BL/6J和apoE-/-小鼠分为C57BL/6对照组、apoE-/-组、apoE-/-+硫氢化钠(NaHS)组和apoE-/-+炔丙基甘氨酸(PPG)组,每组各8只,普通饮食饲养10周。硫电极法测定血清中H2S的含量;ELISA法测定血清中ICAM-1的含量;荧光实时定量RT-PCR法测定主动脉组织中ICAM-1 mRNA的表达。油红O染色观察小鼠主动脉根部斑块面积的变化。结果 与C57BL/6J小鼠相比,apoE-/-小鼠血清中H2S的含量明显下降(P 0.01),血清中ICAM-1的含量和主动脉组织中ICAM-1 mRNA的表达明显升高(P 0.01),主动脉根部出现明显斑块;给予NaHS后,apoE-/-小鼠血清中H2S的含量明显升高(P 0.05),血清和主动脉组织中ICAM-1的表达明显降低(P 0.01和P 0.05),动脉粥样斑块明显缩小(P 0.05);给予PPG后,apoE-/-小鼠血清中H2S的含量明显降低(P 0.05),血清和主动脉组织中ICAM-1的表达明显增高(P 0.05和P 0.01),动脉粥样斑块明显增大(P 0.01)。结论 气体信号分子H2S可明显抑制动脉粥样斑块形成过程中ICAM-1的表达与分泌。

关键词: 硫化氢, 动脉粥样硬化, Apo E基因敲除小鼠, 细胞间粘附分子-1

Abstract: Objective To explore the effect of hydrogen sulfide (H2S) on intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of atherosclerosis in apoE knockout (apoE-/-) mice. Methods 6 week-old C57BL/6J and apoE-/- mice were divided into control C57BL/6J group, apoE-/- group, apoE-/- + sodium hydrosulfide (NaHS, a donor of H2S) group and apoE-/- + DL-propargylglycine (PPG, an inhibitor of H2S synthase). There were 8 mice in each group. They were fed chow diet for 10 weeks. Serum H2S was measured by sulfide electrode-based method, serum ICAM-1 was determined by ELISA and aortic ICAM-1 mRNA was detected by real time polymerase chain reaction. The changes of atherosclerosis plaque size were observed by oil red O staining. Results Compared with control mice, serum H2S level was significantly decreased in apoE-/- mice (P 0.01), while serum ICAM-1 and aortic ICAM-1 mRNA were markedly increased (P 0.01). The atherosclerosis plaque was obvious in apoE-/- mice. Compared with apoE-/- mice, serum H2S level was significantly increased (P 0.05), while serum ICAM-1 and aortic ICAM-1 mRNA were significantly decreased (P 0.01 and P 0.05, respectively), and the area of atherosclerosis plaque was significantly diminished (P 0.05) in apoE-/-+NaHS mice. In apoE-/-+PPG mice, serum H2S level was significantly decreased (P 0.05), while serum ICAM-1 and aortic ICAM-1 mRNA were significantly increased (P 0.05 and P 0.01, respectively), and the size of atherosclerosis plaque was significantly enlarged (P 0.01). Conclusion H2S suppressed the expression and secretion of ICAM-1 during the formation of atherosclerotic plaque.

Key words: hydrogen sulfide, atherosclerosis, Apo E knockout mice, intercellular adhesion molecule-1