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/6 J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-1mRNA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/6 J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-1mRNA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。
Objective To explore the effect of hydrogen sulfide (H2S) on intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of atheroselerosis in apoE knockout (apoE^-/- ) mice. Methods Six week-old C57BL/6J and apoE^-/- mice were divided into control C57BL/6J group, apoE^-/- group, apoE^-/- + sodium hydrosulfide (NariS, 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. Aortic ICAM-1 mRNA was detected by RT-PCR. The changes of atherosclerosis plaque size were observed by oil red O staining. Results Serum H2 Slevel significantly decreased in apoE^-/- mice( P 〈 0. 01 ) ,while serum ICAM-1 and aortic ICAM-1 mRNA markedly increased(P 〈0. 01 ). The atherosclerosis plaque was found in apoE^-/- mice. Compared with apoE^-/- mice, serum H2S level significantly increased (P 〈0. 05), while serum ICAM-1 and aortic ICAM-1 mRNA significantly decreased(P 〈0. 01 and P 〈0. 05, respectively), and the mass of atherosclerosis plaque significantly diminished (P〈0. 05) in apoE^-/- + NariS mice. In apoE^-/- + PPG mice, serum H2S level significantly decreased (P 〈 0. 05 ), while serum ICAM-1 and aortic ICAM-1 mRNA significantly increased (P 〈 0. 05 and P 〈 0. 01, respectively), and the size of atherosclerosis plaque significantly enlarged (P 〈 0. 01 ). Conclusion H2S suppresses the expression and secretion of ICAM-1 during the formation of atherosclerotic plaque.
出处
《基础医学与临床》
CSCD
北大核心
2009年第1期19-23,共5页
Basic and Clinical Medicine
基金
国家自然科学基金(30571971和30630031)
国家杰出青年科学基金(30425010)
国家重点基础研究发展规划(2006CB503807)