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通过减少炎性组织或细胞趋化因子及炎性因子的表达量能将炎症性病理过程抑制在起始阶段.我们通过体外构建人外周血单个核细胞LPS激活的急性炎症模型及内毒素耐受模型,进行噬菌体肽库亲和筛选,ELISA检测与炎性PBMC的结合能力,分泌抑制实验筛选抑制性噬菌体克隆,经趋化抑制、竞争结合及生成抑制实验检测体外活性,大鼠足肿胀及关节炎模型检验多肽体内作用,SqRT-PCR检测趋化因子及TTP的mRNA水平,探讨其作用机制.筛选到的目标多肽CI-S5趋化抑制率达到48.72%,明显抑制噬菌体阳性克隆P15与LPS激活PBMC的结合,动物试验能明显降低大鼠足肿胀及关节炎症.机制研究显示,CI-S5多肽能降低3种趋化因子的表达量,并调节TTP使其表达增加,提示CI-S5能够靶向炎症前期PBMC,为炎症治疗提供了针对早期急性炎症反应的广谱小分子抑制肽.
By reducing the expression of inflammatory cytokines and cytokines and inflammatory cytokines, the inflammatory pathological process can be inhibited in the initial stage.We constructed the acute inflammatory model of LPS-activated human peripheral blood mononuclear cells and endotoxin tolerance Phage peptide library affinity screening, ELISA test and inflammatory PBMC binding capacity, secretion inhibition test screening of inhibitory phage clones, chemotaxis inhibition, competitive binding and generation inhibition test in vitro activity, rat foot swelling and joint Inflammatory model to test the effect of the polypeptide in vivo, SqRT-PCR detection of chemokine and TTP mRNA levels, to explore its mechanism of action.Screening of the target peptide CI-S5 chemotactic inhibition rate of 48.72%, significantly inhibited phage-positive clone P15 and LPS activation PBMC binding, animal experiments can significantly reduce foot swelling and joint inflammation in rats.Mechanism studies show that CI-S5 polypeptide can reduce the expression of three chemokines and regulate the expression of TTP to increase, suggesting that CI-S5 can target To pre-inflammatory PBMC, a broad spectrum of small molecule inhibitory peptides against early acute inflammatory responses is provided for the treatment of inflammation.