Study on Intestinal Barrier Injury in Acute Necrotizing Pancreatitis Induced by L-Arginine in Mice / 胃肠病学

ABSTRACT

Background: Studies have indicated that dysfunction of intestinal barrier is closely related to the occurrence and development of acute necrotizing pancreatitis (ANP). Aims: To investigate the intestinal barrier injury in mice with ANP induced by L-arginine and its mechanism on aggravating ANP. Methods: Thirty C57BL/6 mice were randomly divided into sham-operation (SO) group and ANP group. Mice in ANP group were intraperitoneally injected with 8% L-arginine (4.5 g/kg) twice at an interval of 1 hour, while mice in SO group were intraperitoneally injected with an equal volume of 0.9% NaCl solution. Mice were sacrificed 24, 48, 72 hours after the establishment of ANP. HE staining was used to evaluate the pathological score of pancreas and intestine. Serum amylase, lipase were determined. Inflammatory factors (IL-1β, IL-6, TNF-α) and intestinal permeability (DAO, D-lactic acid, LPS) were measured by ELISA assay. Western blotting was used to detect protein expressions of TLR4, MyD88 in pancreatic tissue and ileal tissue. Results: Compared with SO group, histopathological score of pancreatic tissue and ileal tissue were significantly increased at corresponding-time in ANP group (P<0.05), serum levels of amylase, lipase, inflammatory factors (IL-1β, IL-6, TNF-α) and intestinal permeability (DAO, D-lactic acid, LPS) were significantly increased (P<0.05), protein expressions of TLR4, MyD88 in pancreatic tissue and ileal tissue were significantly increased (P<0.05). Conclusions: Intestinal permeability is increased in ANP mice induced by L-arginine, and the secretion of LPS is increased, which may enhance the intestinal inflammation and systematic inflammation via activating TLR4-MyD88 signaling pathway, thereby aggravating ANP.