Published online Mar 7, 2021. doi: 10.3748/wjg.v27.i9.815
Peer-review started: November 7, 2020
First decision: December 3, 2020
Revised: December 14, 2020
Accepted: February 1, 2021
Article in press: February 1, 2021
Published online: March 7, 2021
Severe acute pancreatitis (SAP) is an abdominal disease characterized by extensive inflammation and tissue necrosis of the pancreas and usually accompanied by multiple organ damage, resulting in high mortality. Intestinal injury is the most common extrapancreatic complication and is closely related to the severity of SAP. Our previous studies proved that elimination of pancreatitis associated ascitic fluids (PAAF) through early abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury and protects intestinal barrier effectively, but the potential molecular mechanisms responsible for the beneficial effect are yet to be clarified.
The inflammatory response plays an essential role in the pathological process of SAP-induced intestinal injury. High concentration of high mobility group box protein 1 (HMGB1) participates in remote organ damage and has been confirmed during SAP. Based on our previous research, we further investigate whether HMGB1 in ascites is related to intestinal inflammation and apoptosis under SAP conditions, which may reveal the underlying mechanism of APD in SAP.
The purpose of the present experiment was to explore the effect of APD treatment on intestinal inflammation and apoptosis induced by SAP in rats, and its potential mechanisms.
SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild acute pancreatitis was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats for APD. Morphological staining, serum amylase, lipase and inflammatory mediators, serum and ascites HMGB1, serum indices which reflect intestinal barrier function, apoptosis and associated proteins in intestinal tissue were assessed. The expression levels of key proteins in the toll-like receptor 4 (TLR4) signaling pathway were also examined.
The results demonstrated that APD notably alleviated the changes in pancrease and intestinal mucosa, attenuated the alterations in serum amylase, lipase and inflammatory mediators, improved intestinal barrier function, lessened intestinal inflammation and accompanying apoptosis of mucosal cells, and reversed the expression of apoptosis-associated proteins. APD significantly inhibited activation of the intestinal TLR4 signaling pathway mediated by HMGB1 in intestinal tissue, and thus plays a protective role in SAP-associated intestinal injury.
APD treatment effectively improved intestinal barrier function, ameliorated the intestinal inflammatory response and mucosa cell apoptosis in rats with SAP. The protective effects are potentially due to the inhibition of the HMGB1-mediated TLR4 signaling pathway.
The present study provided new evidence of the efficacy and safety of APD treatment on SAP, and provided a novel molecular mechanism associated with the effect of APD on SAP-induced intestinal injury. However, in this research we did not detect the expression change of HMGB1 in intestinal tissue. In our next experiments, we will attempt to verify the relationship between intestinal HMGB1 and PAAF to further reveal the precise mechanisms of APD treatment in SAP.