Effect Of Intestinal Autophagy On Bacterial Translocation In Severe Acute Pancreatitis And Its Possible Mechanism

Objective: In severe acute pancreatitis(SAP),enterogenic infection is an important prognostic indicator of late SAP infection,and bacterial translocation(BT)is an important cause of enterogenic infection.At the early stage of SAP,enterogenic infection can cause systemic inflammatory response syndrome(SIRS),which may lead to multiple organ failure(MODS)and sepsis,and it is a major factor of late death in SAP.And the intestinal mucosal barrier injury caused the molecular mechanism of BT was unclear in SAP.Autophagy is involved in the pathophysiological process of many diseases,intestinal epithelial autophagy plays an important role in homeostasis and gut immunity.Increasing studies has shown that autophagy can remove intestinal epithelial invasion of intestinal bacteria,and recent in vitro studies showed that autophagy enhances intestinal epithelial tight junction(TJ)protein expression.However,the effect of intestinal epithelial autophagy on intestinal BT in patients with SAP is unclear.We aimed to investigate the effects of autophagy on the expression of BT and intestinal epithelial TJ in intestinal epithelial cells of patients with SAP.Methods: According to the definition of classification standard of acute pancreatitis revised in 2012 in Atlanta and acute physiology and chronic health evaluation(APACHE-?),thirtyone patients with SAP were enrolled from the APACHE-? score between 8 to 12,and 8 healthy people were enrolled as healthy control(HC).Based on the SAP 16 S r DNA sequencing in peripheral blood of patients with SAP,according to the results of determination that were in the peripheral blood of patients with or without bacterial DNA,SAP patients divided into bacterial translocation positive group BT(+)and negative bacterial translocation group BT(-),at the same time using colonoscopy to obtain colonic epithelial tissue in SAP patients and healthy human(HC).Serum endotoxin level was measured by enzyme linked immunosorbent assay(ELISA).Tight junction protein Zonula occluden-1(ZO-1),claudins-2(CL-2),occludin(OC)and autophagy marker protein microtubule associated protein 1 light chain 3(LC3?)were detected by immunoblotting technique(Western blot).Results: Among the 31 patients with SAP,bacterial DNA were detected in peripheral blood samples of 14 patients,and the positive ratio was(45.2%).In patients with SAP in BT(+)detection of serum endotoxin level was significantly higher than that of BT(-)and HC group(P < 0.05,P < 0.05),and CL-2 protein expression level in BT(+)was higher than BT(-)group and HC group(P < 0.05,P < 0.05).TJ protein OC and ZO-1 in BT(+)group was lower than that of BT(-)patients.In addition,in patients with SAP of autophagy related protein LC3 ? expression level was higher than that of group HC(P < 0.05).Moreover,intestinal epithelial LC3? in BT(-)patients was higher than that of BT(+)patients(P < 0.05),and CL-2 was negatively correlated with the expression of LC3? in patients with SAP(r =-0.71,P < 0.05),the opposite was that ZO-1 and OC was positively correlated LC3 ? expression(r = 0.79,P < 0.01;r = 0.88,P < 0.01).Conclusion: Intestinal epithelial autophagy was activation in SAP patients,and activation of intestinal epithelial autophagy may reduce the incidence of bacterial translocation,which mechanism of effects of intestinal epithelial autophagy on intestinal epithelial tight junction may be to reduce the incidence of bacterial translocation.