Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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ISSN 1899–5276 (print),   ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 8, August, p. 1059–1066

doi: 10.17219/acem/99910

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Effect of PI3K/PKB signal pathway inhibitor wortmannin pretreatment on intestinal barrier function in severe acute pancreatitic rats

Qinqing Tang1,C,D, Hengyi Wang1,B,C, Xingyu Wang1,C, Maoyong Fang1,E, Hong Zhang1,A,F

1 Department of Emergency, First Affiliated Hospital of Anhui Medical University, Hefei, China

Abstract

Background. It is well-known that severe acute pancreatitis (SAP) due to infection is mainly caused by intestinal bacterial translocation. The intestinal barrier is tasked with preventing intestinal pathogenic bacteria and toxins from reaching the parenteral tissues through the intestinal wall. Therefore, maintaining intestinal barrier function may be the key to preventing damage from acute pancreatitis (AP). The phosphatidylinositol 3-kinase/protein kinase B pathway (PI3K/PKB) plays a role in AP. However, the exact effect of PI3K/PKB on injury associated with SAP has not yet been found.
Objectives. The present study was aimed at investigating the impact of wortmannin (WT), a PI3K/PKB inhibitor, on intestinal barrier function in SAP rats.
Material and Methods. The rats were divided into 3 groups: 1) the Sham Surgery group (SS), whose duodenum and pancreas were flipped 3 times (n = 18); 2) the pancreatitis group (SAP), who were injected through retrograde pancreatic duct injection with 5% sodium taurocholate (n = 18); and 3) the WSAP intervention group (SAP+WT). Serum alpha-amylase levels, plasma endogenous endotoxin, hematoxylin-eosin (H&E) staining, intestinal mucosa electron microscopy, intestinal permeability, and expression of p-PKB (phosphorylated protein kinase B) were measured.
Results. In our findings under an electron microscope, the SAP group presented cell edema and mitochondrial vacuolated degeneration, sparsely arranged microvilli, tight junction damage, and widening, while the WSAP group exhibited less change and lower pancreas scores (7.4 ±1.14, 10.2 ±1.48 and 12.0 ±1.58 for 3 h, 6 h and 12 h, respectively) (p < 0.05). Furthermore, the plasma endogenous endotoxin levels and Evans blue content of the WSAP group was significantly lower at all timepoints than in the SAP group (p < 0.05). Western blotting showed that p-PKB expression was lower in the WSAP group than in the SAP group (p < 0.05). Our study suggests that WT relieves intestinal permeability changes in SAP rats and may be dose-dependent.
Conclusion. The PI3K/PKB signal pathway may involve SAP-related intestinal injuries and WT may relieve SAP intestinal injuries through the PI3K/PKB pathway.

Key words

intestinal barrier, alpha-amylase, endotoxin, acute pancreatitis, signal pathway, wortmannin

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