硫化氢在载脂蛋白E基因敲除小鼠动脉粥样硬化病变发展中的作用。
Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice.
作者信息
Wang Yanfei, Zhao Xia, Jin Hongfang, Wei Hongling, Li Wei, Bu Dingfang, Tang Xiuying, Ren Yali, Tang Chaoshu, Du Junbao
机构信息
Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West district, Beijing 100034, PR China.
出版信息
Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):173-9. doi: 10.1161/ATVBAHA.108.179333. Epub 2008 Nov 6.
OBJECTIVE
We explored the effect of hydrogen sulfide (H(2)S) on atherosclerotic progression, particularly on intracellular adhesion molecule-1 (ICAM-1) in apolipoprotein-E knockout (apoE(-/-)) mice and human umbilical vein endothelial cells (HUVECs).
METHODS AND RESULTS
ApoE(-/-) mice were treated with sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG); HUVECs were pretreated with NaHS. Compared with control mice, apoE(-/-) mice showed decreased plasma H(2)S level and aortic H(2)S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE(-/-) mice, apoE(-/-)+NaHS mice showed increased plasma H(2)S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE(-/-)+PPG mice showed decreased plasma H(2)S level but enlarged plaque size and increased plasma and aortic ICAM-1 levels. NaHS suppressed ICAM-1 expression in tumor necrosis factor (TNF)-alpha-treated HUVECs. NaHS inhibited IkappaB degradation and NF-kappaB nuclear translocation in HUVECs treated with TNF-alpha.
CONCLUSIONS
The vascular CSE/H(2)S pathway was disturbed in apoE(-/-) mice. H(2)S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE(-/-) mice. H(2)S inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kappaB pathway.
目的
我们探讨了硫化氢（H₂S）对动脉粥样硬化进展的影响，特别是对载脂蛋白E基因敲除（apoE⁻/⁻）小鼠和人脐静脉内皮细胞（HUVECs）中细胞间黏附分子-1（ICAM-1）的影响。
方法与结果
用硫氢化钠（NaHS）或DL-炔丙基甘氨酸（PPG）处理apoE⁻/⁻小鼠；用NaHS预处理HUVECs。与对照小鼠相比，apoE⁻/⁻小鼠血浆H₂S水平和主动脉H₂S生成减少，但血浆ICAM-1以及主动脉ICAM-1蛋白和mRNA增加。与apoE⁻/⁻小鼠相比，apoE⁻/⁻ + NaHS小鼠血浆H₂S水平升高，但动脉粥样硬化斑块大小减小，血浆和主动脉ICAM-1水平降低，而apoE⁻/⁻ + PPG小鼠血浆H₂S水平降低，但斑块大小增大，血浆和主动脉ICAM-1水平升高。NaHS抑制肿瘤坏死因子（TNF）-α处理的HUVECs中ICAM-1的表达。NaHS抑制TNF-α处理的HUVECs中IκB的降解和NF-κB的核转位。
结论
apoE⁻/⁻小鼠的血管CSE/H₂S途径受到干扰。H₂S在apoE⁻/⁻小鼠中发挥抗动脉粥样硬化作用并抑制ICAM-1表达。H₂S通过NF-κB途径抑制TNF-α诱导的HUVECs中ICAM-1的表达。
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