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作 者:张彦峰[1] 莫红缨[1] 刘晓青[1] 何为群[1] 黎毅敏[1]
机构地区:[1]广州医学院第一附属医院广州呼吸疾病研究所,510120
出 处:《国际呼吸杂志》2009年第13期769-771,F0003,共4页International Journal of Respiration
基 金:基金项目:广东省自然科技基金项目(061109)
摘 要:目的研究髓系细胞触发受体1(triggering receptor expressed on myeloid cell-1,TREM-1)结合多肽对脓毒症小鼠保护作用。方法经噬菌体表面展示肽库筛选出的TREM-1结合多肽,42只健康雄性Balb/c小鼠随机分为空白组,脂多糖(LPS)组,对照1(多肽)组,对照2(LPS+TREM-1单抗)组,对照3(LPS+多肽+TREM-1单抗)组,早期治疗(LPS+LPS前1h多肽)组,延迟治疗(LPS+LPS后4h多肽)组,各组分别于设定时间点麻醉处死小鼠,取肝组织提mRNA行逆转录、荧光定量PCR检测TREM-1、肿瘤坏死因子α(TNF—α)、白介素1β(IL-1β)mRNA表达水平,并取肺组织病理组织学观察。结果LPS能增加小鼠肝细胞TREM-1mRNA表达,早期治疗组可抑制LPS引起的肝组织TNF—α、IL-1βmRNA增加且能减轻LPS导致的肺病理组织炎症反应而延迟治疗组并未见以上抑制作用,此抑制作用能为TREM-1单抗所拮抗。结论LPS诱导的脓毒症可见TREM-1mRNA表达上调。TREM-1结合多肽对脓毒症小鼠具有保护作用,阻断TREM-1介导的全身炎症反应综合征可能是其发挥作用的机制。Objective To study the influence of triggering receptor expressed on myeloid cell-1 (TREM-1) binding peptide on lipopolysaccharide (LPS)-induced sepsis in mice. Methods Mice sepsis models were established by LPS through peritoneal injection. Mice were divided into blank, LPS-induced sepsis,binding peptide, LPS+ TREM-1 monoclonal antibody, LPS+ TREM-1 monoclonal antibody + binding peptide protection,early binding peptide protection and delayed binding peptide protection. Lung and liver were obtained at the set time. The level of liver TREM-1, TNF-α, IL-1β mRNA were determined by quantitative reverse transcriptional polymerase chain reaction. Detection of histology for lung was carried out. Results TREM-1 mRNA increased while the mice were treated with LPS. The early binding peptide protection could decrease the liver TNF-α, IL-1β mRNA, reducing lung histological damage, which was inhibited by TREM-1 monoclonal agonist antibodies and not detected in the delayed protection group. Conclusions Treating the mice with LPS resulted in increased level of TREM-1 mRNA. TREM-1 binding peptide has obviously protective effect on LPS-induced sepsis in mice. The blockage of SIRS induced by TREM-1 may be a new pathway for the treatment of sepsis.
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