Early changes of urine proteome in a diethyldithiocarbamate-induced chronic pancreatitis rat model

• 1、Gene Engineering Drug and Biotechnology Beijing Key Laboratory,Beijing Normal University， Beijing 100875

Abstract：Biomarkers are measurable changes associated with the disease. Without homeostasis mechanisms, theoretically urine accumulates early changes and can be better and earlier biomarker source than blood especially for chronic diseases. Chronic pancreatitis is a chronic inflammatory disease characterized by pancreatic fibrosis as a major pathological change. If diagnosed earlier, effective preventive measures may be used. This study tests if early changes can be detected in rat model of chronic pancreatitis induced by intraperitoneal injection of diethyldithiocarbamate. Urine samples before injection and 2 weeks, 3 weeks and 4 weeks after injection were collected. Urinary proteins from three rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with before injection, the urinary patterns have changed significantly in all three rats. At week 2, fifteen differential proteins, which three increased and twelve decreased, were identified when there was no obvious pathological changes yet. Twelve of these differential proteins were altered at other two time points and five proteins had previously been associated with chronic pancreatitis. At week 3, twenty-nine differential proteins were identified, when inflammatory cytokines infiltration, acinar disruption, and slight fibrosis occurred. Significant fibrosis detected at week 4 and thirty-eight differential proteins were identified. At the stages of week 3 and week 4, fourteen urinary proteins had been reported to deferentially expressed in the serum or pancreatic tissue of chronic pancreatitis patients and other animal model studies. These findings demonstrate that changes caused by chronic pancreatitis can be reflected early in urinary proteins. New clues in early diagnosis of chronic pancreatitis can be found with only small number of modeled animals.

Keywords： proteomics urine chronic pancreatitis biomarkers