Serum microRNAs-217 and −375 as biomarkers of acute pancreatic injury in rats

Pancreatic injury in rats is primarily detected through histopathological changes and conventional serum biomarkers such as amylase and lipase. However, amylase and lipase have a short half-life and are markers of acinar, not islet cell injury. We investigated whether circulating microRNA (miR) levels that are enriched in acinar cells (miR-217, miR-216a/b) or islet cells (miR-375) could serve as markers of pancreatic injury. Rats were treated with a single dose of either vehicle, streptozotocin (STZ), caerulein, or acetaminophen (APAP), and necropsied at 4, 24, and 48 h. Pancreas, liver, heart, kidney and skeletal muscle were analyzed for histopathology. Blood was collected at necropsy and processed to serum for amylase/lipase enzymatic determinations and miR qPCR analysis. Caerulein induced degeneration/necrosis of acinar cells at 4 h that persisted for 48 h. Caerulein-induced injury was associated with increases in serum amylase/lipase (4 h), miR-216a/b (4, 24 h). In contrast, serum miR-217 was detected at all time points examined. STZ did not induce increases in either amylase or lipase but did induce increases in miR-375 levels at 4 and 24 h. No increases in miR-375 were observed in caerulein-treated rats, and no increases were observed in miR-217 and miR-216a/b in STZ-treated rats. APAP induced centrilobular necrosis in the liver 24 h after treatment, but did not induce pancreatic injury or increases in miR-217 or miR-375. Our results suggest that miR-217 and miR-375 represent promising biomarkers of pancreatic injury in rats.