Effects of Bacterial Translocation and Autophagy on Acute Lung Injury Induced by Severe Acute Pancreatitis

Abstract

Aim. To reveal the role of bacterial translocation (BT) and autophagy in severe acute pancreatitis-induced acute lung injury (SAP-ALI). Methods. Rats were separated into a control (sham-operation) group (n=10) and a SAP group (n=30). Sodium taurocholate (5%) was retrogradely injected into the cholangiopancreatic duct to induce SAP-ALI in rats. Then, 16S rDNA sequencing was used to detect bacterial translocation (BT). Hematoxylin eosin staining (HE) was used to detect morphological changes to the pancreas, intestine, and lung. And lung tissue wet/dry weight ratio (W/D ratio) was used to assess the extent of pulmonary edema. The expressions of LC3II and Beclin1 proteins were analyzed by western blot and immunofluorescence. Glutathione peroxidase (GPx), malondialdehyde (MDA), and superoxide dismutase (SOD) were used to assess oxidative stress in lung tissue. Results. Levels of TNF-α, IL-6, lipase, and amylase in the SAP group were significantly higher than those in the control group (P<0.01). Histopathological score and W/D ratio of the lung in the SAP-BT(+) group were significantly higher than that in the SAP-BT(-) group (P<0.01). LC3II expression was higher in the SAP-BT(-) group than that in the SAP-BT(+) group (P<0.01). The results were consistent with those of LC3II immunofluorescence assay. The expression of Beclin1 was similar to that of LC3II (P<0.01). MDA content in the SAP-BT(+) group was significantly higher than that in the SAP-BT(-) group (P<0.01), whereas SOD and GPX activities were opposite (P<0.01). Conclusions. BT can aggravate SAP-ALI with the increasing oxidative stress level, which may be related to the decrease of autophagy level.

A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management

“…Consequently, clarification of the process of impaired autophagy early in AP could provide a new target for clinical exploration for novel AP drugs. Oxidative stress is also increased due to bacterial translocation, which further aggravates AP-associated lung injury, this process may be related to decreased autophagy level (63). The AP models of IL-22 transgenic mice and IL-22 recombinant adenovirus mice induced by caerulein confirmed that IL-22 can prevent the formation of autophagosomes through the Beclin-1 pathway, thereby reducing the severity of AP (64).…”

Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis

“…This process also enhances the secretion of inflammatory molecules including IL-6 and TNF-α. 192 , 193 In addition, there is a positive correlation between the abundance of Enterobacter, Enterococcus and the expression of inflammatory factors (IL-6 and TNF-α), suggesting the role of pathogenic bacteria in accelerating the inflammatory responses under SAP-ALI. 188 The relative abundance of Bacteroides and Prevotella , which are important SCFAs-producing bacteria, decreased during SAP, resulting in the reduction of propionate, butyrate and valerate.…”

The Pathogenesis of Pancreatitis and the Role of Autophagy

“…Reduced autophagy in severe AP impairs tight and gap junctions and reduces the function of goblet and Paneth cells, leading to increased bacterial translocation and extra-pancreatic serious manifestations [370,378,379]. The increase in oxidative stress associated with the increased bacterial translocation will aggravate AP-associated lung injury and was attributed to decreased autophagy levels [380]. However, the opposite has also been reported, as excessive autophagy may also be connected to lung injury.…”