Yang Yongbi, Zhang Teng, Cao Hongxue, Yu Dan, Zhang Tong, Zhao Shaojuan, Jing Xiaohui, Song Liying, Liu Yunye, Che Ruixiang, Liu Xin, Li Deshan, Ren Guiping
Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, PR China.
Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, Heilongjiang Province, PR China.
Biomed Pharmacother. 2017 Aug;92:905-912. doi: 10.1016/j.biopha.2017.05.147. Epub 2017 Jun 9.
Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Recently, our study found that a bispecific fusion protein treatment can ameliorate the lung injury induced by LPS. However, the molecular mechanisms which bispecific fusion protein ameliorates acute lung injury remain unclear. In this study, we found that the bispecific fusion protein treatment inhibited the nuclear transcription of NF-κB in confocal laser scanning fluorescence microscopy, the bispecific fusion protein exert protective effects in the cell model of ALI induced by lipopolysaccharide (LPS) via inhibiting the nuclear factor κB (NF-κB) signaling pathway and mediate inflammation. Moreover, the treatment of the bispecific fusion protein show its efficacy in animal models stimulated by LPS, the results of real-time PCR and ELISA demonstrate that bispecific fusion protein treatment effectively inhibited the over-expression of inflammatory cytokines(tumor necrosis factor α, interleukin 1β and interleukin 17). In addition, LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology, which was meliorated by bispecific fusion protein treatment. Collectively, these results demonstrate that bispecific fusion protein treatment ameliorates LPS-induced ALI through reducing inflammatory cytokines and lung inflammation, which may be associated with the decreased the nuclear transcription of NF-κB. The bispecific fusion protein may be useful as a novel therapy to treat ALI.
急性肺损伤（ALI）仍是危重症患者发病和死亡的主要原因。最近，我们的研究发现双特异性融合蛋白治疗可改善脂多糖（LPS）诱导的肺损伤。然而，双特异性融合蛋白改善急性肺损伤的分子机制仍不清楚。在本研究中，我们发现双特异性融合蛋白治疗在共聚焦激光扫描荧光显微镜下抑制了核因子κB（NF-κB）的核转录，双特异性融合蛋白通过抑制核因子κB（NF-κB）信号通路并介导炎症反应，在脂多糖（LPS）诱导的ALI细胞模型中发挥保护作用。此外，双特异性融合蛋白治疗在LPS刺激的动物模型中显示出疗效，实时PCR和ELISA结果表明，双特异性融合蛋白治疗有效抑制了炎性细胞因子（肿瘤坏死因子α、白细胞介素1β和白细胞介素17）的过度表达。此外，LPS攻击的小鼠表现出明显的肺损伤，其特征为组织病理学恶化，而双特异性融合蛋白治疗可改善这种情况。总的来说，这些结果表明，双特异性融合蛋白治疗通过减少炎性细胞因子和肺部炎症来改善LPS诱导的ALI，这可能与NF-κB的核转录减少有关。双特异性融合蛋白可能作为一种治疗ALI的新疗法。
