Effect and mechanism of vagus nerve electrical stimulation on intestinal permeability in sepsis mice

Objective To investigate the effect and mechanism of vagus nerve electrical stimulation on intestinal permeability in sepsis mice.

Methods Fifty C57BL/6 mice were randomly divided into control group (CON group), sepsis group lipopolysaccharide (LPS) group, vagus nerve transection group (VGX group), vagus nerve electrical stimulation group (STM group), and α-bungarotoxin (α-BGT) group, with 10 mice in each group. The LPS group, VGX group, STM group, and α-BGT group were injected intraperitoneally with 10 mg/kg LPS to prepare the sepsis model, while the CON group was injected intraperitoneally with an equal volume of normal saline. The bilateral cervical vagus nerves were exposed only in the CON and LPS groups, while they were transected in the VGX, STM, and α-BGT groups. In the STM group, the left cervical vagus nerve was electrically stimulated, and α-BGT was injected subcutaneously before electrical stimulation of the left cervical vagus nerve in the α-BGT group. The ileum tissues were collected from mice in each group after euthanasia, and were performed histopathological observations under a light microscope to evaluate intestinal tissue permeability and detect the relative expression levels of tight junction proteins (ZO-1, claudin-2), myosin light chain kinase (MLCK), and nuclear factor-κB (NF-κB) proteins.

Results The ileal mucosa epithelial cells in the LPS group were severely damaged, with necrosis and shedding of microvilli and massive inflammatory cell infiltration. The degree of histopathological changes in the ileum tissue in the VGX group was more severe than in the LPS group, while was less severe in the STM group compared to the LPS and VGX groups. The intestinal mucosa epithelial cells were most severely damaged in the α-BGT group. Compared with the CON group, the intestinal epithelial tissue permeability was increased in the LPS and VGX groups (P < 0.05). Compared with the LPS and VGX groups, the intestinal epithelial tissue permeability was decreased in the STM group (P < 0.05). Compared with the STM group, the intestinal epithelial tissue permeability was increased in the α-BGT group (P < 0.05). The relative expression levels of ZO-1 and claudin-2 proteins in the intestinal epithelial tissues were lower in the LPS and VGX groups than in the CON group, while they were higher in the STM group compared to the LPS and VGX groups, meanwhile, they were lower in the α-BGT group than in the STM group (P < 0.05). The relative expression levels of MLCK and NF-κB proteins in the intestinal epithelial tissues were higher in the LPS and VGX groups than in the CON group, while they were lower in the STM group compared to the LPS and VGX groups, and were higher in the intestinal epithelial tissues in the α-BGT group than in the STM group(P < 0.05).

Conclusion Electrical stimulation of the vagus nerve helps protecting the intestinal barrier function in sepsis mice, and its potential mechanism may be related to the activation of the cholinergic anti-inflammatory pathway that further inhibits the inflammatory response.