Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages

Abstract

AIMTo investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP).METHODSSAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.RESULTSAPD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.CONCLUSIONThese findings suggest that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.

CircRNA Expression Profiles and the Potential Role of CircZFP644 in Mice With Severe Acute Pancreatitis via Sponging miR-21-3p

“…The method of model preparation is similar to that we previously reported (Liu et al, 2018). Briefly, mice were randomly divided into control group and SAP group and anesthetized with 5% isoflurane (via induction box) prior to surgery.…”

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

“…After puncture needle and arterial clip were removed, the model was successfully constructed following the closure of abdomen. In APD group, a drainage tube with vacuum bulb was implanted in its right lower abdomen immediately after SAP induction [10]. No operation was performed in the SO group except abdominal opening and closing.…”

“…toxic substances such as tumor necrosis factor, interleukin, endotoxin and so on [2][3][4][5]. Our previous clinical and experimental studies showed that abdominal paracentesis drainage (APD) attenuated the outcomes of SAP safely and effectively through removing PAAF [6][7][8][9][10]. However, little is known about the underlying mechanisms responsible for APD treatment for SAP.…”

The Role of Pancreatic Infiltrating Innate Immune Cells in Acute Pancreatitis

“…Since the polarization status of macrophages is related to the progression and severity of AP, many researchers have focused on the therapeutic effect of regulating the polarization status of macrophages on AP 48 , 91 , 121 , 122 . It is generally accepted that abdominal paracentesis drainage (APD) can alleviate AP.…”