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2008年日本学者曾经报道连续饮用6月氢气水能对抗先天性基因缺陷引起的小鼠动脉硬化,该论文属于氢气医学领域比较早期的研究。但该研究相对比较简单,没有在分子机制上做任何探讨。最近关于其机制有了新的报道。来自中国山东泰山医院院动脉粥样硬化研究所秦树存教授的团队,采用细胞和基因敲除小鼠证明氢气能通过抑制内皮细胞NFkappaB活性抑制肿瘤坏死因子诱导的凝集素样氧化LDL受体1表达。
关于 LOX-1的背景资料:低密度脂蛋白(oxidized low density lipop rotein, ox2LDL)的特异性受体———血凝素样ox2LDL 受体1 ( lectin2likeoxi2 dized low density lipop rotein recep tor21,LOX21)可通过损伤血管内皮,促进炎症反应,加速细胞凋亡和泡沫细胞形成等机制促进动脉粥样硬化的发展,进而导致冠心病的发生、发展。炎症因子、一氧化氮缺乏等因素可促进LOX-1表达,一些相关药物通过抑制LOX-1的表达在动脉粥样硬化中起作用,为临床抗动脉粥样硬化治疗提供新的途径。因此这个受体是研究动脉硬化的关键分子。
研究摘要:氢气是一种良好的生物抗氧化物质,氧化型低密度脂蛋白通过结合细胞表面受体
LOX-1在动脉硬化的发生过程中具有重要作用。多种刺激因子如TNF-a可以促进 LOX-1的表达。本研究各种刺激因子诱导内皮细胞的LOX-1表达上调是否可以被氢气阻断。结果发发现,氢气对TNF-a等各种刺激因子引起的内皮细胞LOX-1基因表达和蛋白水平上调均具有显著的抑制作用,NF-kB的抑制剂 NAC对TNF-a引起的内皮细胞LOX-1基因表达和蛋白水平上调同样具有抑制作用。氢气对TNF-a引起的内皮细胞NF-k B激活和IkB-a磷酸化具有抑制作用。氢气对apo E基因敲除动脉硬化小鼠的LOX-1表达和NF-kB活性也具有抑制作用。因此氢气可能通过抑制NF-k B对减少炎症因子诱导的LOX-1表达,发挥对动脉硬化的治疗作用。该研究更深入地研究了氢气治疗疾病的分子机制,并采用基因敲除动脉验证了细胞水平上的结果,丰富了人们对氢气治疗疾病的分子机制的认识,确定了氢气抗炎症的分子途径。是一篇非常重要的研究报道。全文:
H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inh.pdf
H2 inhibits TNF-a-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor kB activation in endothelial cells
Guohua Song • Hua Tian • Jia Liu • Hongle Zhang • Xuejun Sun • Shucun Qin
Abstract H2 is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cellsurface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-a. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H2 in endothelial cells. H2 significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-a, at the protein and mRNA levels. The TNF-ainduced upregulation of LOX-1 was also attenuated by the NF-kB inhibitor N-acetyl-L-cysteine. H2 inhibited the TNF-a-induced activation of NF-kB and the phosphorylation of IkB-a. Furthermore, H2 inhibited the expression of LOX-1 and the activation of NF-kB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H2 probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-kB activation.
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