Proteomics analysis based upon TNBS-induced UC model rats

Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats’ model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

溃疡性结肠炎（Ulcerative Colitis, UC）是一类以结肠黏膜连续性弥漫性炎症改变为特征的慢性非特异性炎性肠病，亟需新型治疗方案。光动力疗法（Photodynamic Therapy, PDT）作为一种极具前景的理化治疗手段，本研究采用新型光敏剂LD4介导的光动力疗法，干预2,4,6-三硝基苯磺酸（2,4,6-Trinitrobenzene Sulfonic Acid, TNBS）诱导的UC大鼠模型，探究其治疗效果与作用机制。实验结果表明，LD4-PDT可提升该模型大鼠的存活率，下调白细胞介素（Interleukin, IL）-6、IL-1、肿瘤坏死因子（Tumor Necrosis Factor, TNF）-α、丙二醛（Malondialdehyde, MDA）、髓过氧化物酶（Myeloperoxidase, MPO）的表达水平，上调谷胱甘肽（Glutathione, GSH）与超氧化物氧化酶（Superoxide Oxidase, SOD）的表达，同时维持肠上皮结构的完整性。此外，LD4-PDT治疗可重塑TNBS诱导大鼠的肠道菌群组成，并将结肠蛋白质组谱重编程至近乎正常状态。基于该UC模型大鼠的蛋白质组学分析显示，含铜胺氧化酶1（Amine Oxidase Copper-containing 1, AOC1）是LD4-PDT的潜在作用靶点。综上，新型光敏剂LD4介导的光动力疗法有望成为UC的高效治疗手段，而AOC1或为颇具潜力的治疗靶点。