Overexpression of miR-99a Alleviates Intestinal Mucosal Barrier Injury in Rats with Severe Acute Pancreatitis
Severe acute pancreatitis (SAP), which is characterized by acute onset and high mortality, is complicated with systemic inflammatory response syndrome. This study investigated the molecular mechanism underlying SAP-induced intestinal mucosal barrier injury. SAP was established in rats by retrograde injection of sodium taurocholate (STC) into biliopancreatic duct. Transfection of miR-99a mimic was conducted 24 h before the SAP establishment. Histological properties of pancreatic and intestinal tissues were observed by hematoxylin-eosin staining. The serum levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, procalcitonin (PCT), endotoxin (ET), and diamine oxidase (DAO) were measured by enzyme-linked immunosorbent assay. The expressions of miR-99a, NADPH oxidase (NOX)4, zonula occludens (ZO)-1, occludin, and claudin-1 in pancreatic and the intestinal tissue were determined by quantitative reverse transcription polymerase chain reaction or Western blot. STC injection damaged pancreatic and intestinal tissues of the rats. During the model construction, the serum levels of IL-1β, TNF-α, PCT, ET, and DAO were increased, whereas miR-99a expression in pancreatic and intestinal tissues of the rats was decreased. miR-99a mimic alleviated SAP-induced histological abnormality of pancreatic and intestinal tissues; moreover, it reversed the serum levels of IL-1β, TNF-α, PCT, ET, and DAO increased by SAP, decreased SAP-increased NOX4 expression and increased the expressions of ZO-1, occludin, and claudin-1 previously decreased by SAP in pancreatic and the intestinal tissues. Thus, overexpressed miR-99a could alleviate intestinal mucosal barrier injury in rats with SAP.
Keywords: NOX4; intestinal mucosal barrier injury; miR-99a; severe acute pancreatitis.