Study on the VSAP phosphorylation mediating the tight junction protein to protect the intestinal epithelial barrier function in sepsis

Objective To verify that the tight junction proteins ZO-1, Claudin-5 and Occludin in protecting intestinal barrier function in sepsis were associated with vasodilator-stimulated phosphoprotein(VASP).

Methods A mouse model of sepsis was constructed by cecum ligation perforation, and the rats were divided into the control group, sham-operated group, model group and Bucladesine of VASP phosphorylation agonist group.The serum levels of diamine oxidase(DAO) and D-lactic acid(D-LA) were measured by ELISA.HE staining was performed to observe the histomorphology of the small intestinal mucosa.TUNEL staining was used to detect the apoptosis of small intestinal epithelial cells.Bax, Bcl-2, p-VASP, ZO-1, Occludin and claudin-5 protein expression levels were detected by Western blotting.

Results Compared with the control and sham-operated groups, the number of small intestinal villi reduced, the villi broken, the TUNEL-positive cells increased, the levels of DAO and D-LA significantly increased(P < 0.05), the levels of p-VASP protein expression significantly increased(P < 0.05), and the levels of ZO-1, Occludin and claudin-5 protein expression significantly decreased in the model group(P < 0.05).Compared with the model group, the number of small intestinal villi increased, the villi breakage decreased, the TUNEL-positive cells decreased, the DAO and D-LA content significantly decreased(P < 0.05), the p-VASP and Bax protein expression levels significantly decreased(P < 0.05), and the expression levels of ZO-1, Occludin, claudin-5 and Bcl-2 protein increased in the Bucladesine group(P < 0.05).

Conclusions The function of small intestinal epithelial barrier recovers after inhibiting the p-VASP in sepsis mice, which is related to up-regulation of tight junction protein expression.