Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing 100875, China.
Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing 100875, China.
J Proteomics. 2018 Aug 30;186:8-14. doi: 10.1016/j.jprot.2018.07.015. Epub 2018 Jul 22.
Without homeostasis mechanisms, urine accumulates early changes in biomarkers and can be a better and earlier biomarker source than blood, especially for chronic diseases. This study tests whether early changes can be detected in a rat model of chronic pancreatitis induced by intraperitoneal injection of diethyldithiocarbamate. Urinary proteins from three rats were profiled by liquid chromatography coupled with tandem mass spectrometry. Compared with before injection, fifty differential proteins that had human orthologs were significantly changed in the chronic pancreatitis rats. At week 2, fifteen differential proteins were identified when no obvious pathological changes had yet appeared. Among them, twelve proteins were altered at the other two time points, five had previously been associated with chronic pancreatitis. Inflammatory cytokines infiltration, acinar disruption and fibrosis were detected at week 3 and week 4, at which points fourteen identified differential proteins had been reported to be differentially expressed in the serum or pancreatic tissue of chronic pancreatitis patients and other animal model studies. These include proteins that are significant in acute-phase response (FETUA, F2, FINC and REG3G), extracellular matrix organization (COMP, FINC) and tissue remodeling (CSPG4, GAS6). REG3G has been described abnormally expressed in several human digestive system diseases such as chronic pancreatitis.
This study demonstrate that changes caused by chronic pancreatitis can be reflected early in urinary proteins. New clues for the early diagnosis of chronic pancreatitis can be found even with only the small number of model animals used.
如果没有体内平衡机制，尿液会较早地积累生物标志物的变化，并且可以成为比血液更好和更早的生物标志物来源，尤其是对于慢性疾病。本研究测试了腹腔注射二乙基二硫代氨基甲酸盐诱导的慢性胰腺炎大鼠模型中是否可以检测到早期变化。通过液相色谱串联质谱法对 3 只大鼠的尿液蛋白进行了分析。与注射前相比，慢性胰腺炎大鼠中 50 种具有人类同源物的差异蛋白明显改变。在第 2 周时，当尚未出现明显的病理变化时，鉴定出 15 种差异蛋白。其中，在另外两个时间点，有 12 种蛋白发生了改变，其中 5 种以前与慢性胰腺炎有关。在第 3 周和第 4 周检测到炎症细胞因子浸润、腺泡破坏和纤维化，此时已经报道了 14 种鉴定出的差异蛋白在慢性胰腺炎患者的血清或胰腺组织以及其他动物模型研究中存在差异表达。其中包括在急性相反应（FETUA、F2、FINC 和 REG3G）、细胞外基质组织（COMP、FINC）和组织重塑（CSPG4、GAS6）中具有重要意义的蛋白质。REG3G 在几种人类消化系统疾病（如慢性胰腺炎）中被描述为异常表达。
本研究表明，慢性胰腺炎引起的变化可以较早地反映在尿液蛋白中。即使只使用了少量的模型动物，也可以找到慢性胰腺炎早期诊断的新线索。
