Wen Ai-qing, Yang Qing-wu, Li Jing-cheng, Lv Feng-ling, Zhong Qi, Chen Cai-yu
Department of Neurology, Daping Hospital, The Third Military Medical University, Daping Changjiang Branch Road No. 10, Chongqing 400042, China.
Biochem Biophys Res Commun. 2009 Apr 24;382(1):140-4. doi: 10.1016/j.bbrc.2009.02.152. Epub 2009 Mar 3.
A growing number of researchers have recognized the importance of using lipopolysaccharide (LPS) as target for the prevention and treatment of sepsis. However, no drugs targeting LPS have been applied clinically. In this study, LPS-inhibiting aptamers were screened by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and their therapeutic effects for experimental sepsis were observed. After 12 rounds of screening, 46 sequences were obtained. Primary structure analysis indicated that they had identical sequences, partly conserved sequences, or non-conserved sequences. Secondary structure analysis showed these sequences usually contained hairpin or stem-loop structures. Aptamer 19 significantly decreased NF-kappaB activation of monocytes challenged by LPS and reduced the IL-1 and TNF-alpha concentration in the media of LPS-challenged monocytes. Furthermore, aptamer 19 significantly increased the survival rate of mice with endotoxemia. The results suggest that a novel LPS antagonizing aptamer was obtained by SELEX, which successfully treated experimental sepsis.
越来越多的研究人员已经认识到将脂多糖(LPS)作为脓毒症预防和治疗靶点的重要性。然而,目前尚无针对LPS的药物应用于临床。在本研究中,通过指数富集的配体系统进化技术(SELEX)筛选出了抑制LPS的适配体,并观察了它们对实验性脓毒症的治疗效果。经过12轮筛选,获得了46个序列。一级结构分析表明,它们具有相同序列、部分保守序列或非保守序列。二级结构分析显示,这些序列通常包含发夹或茎环结构。适配体19显著降低了受LPS刺激的单核细胞的NF-κB激活,并降低了LPS刺激的单核细胞培养基中IL-1和TNF-α的浓度。此外,适配体19显著提高了内毒素血症小鼠的存活率。结果表明,通过SELEX获得了一种新型的LPS拮抗适配体,其成功治疗了实验性脓毒症。