Mitochondrial division inhibitor Mdivi-1 protects intestinal barrier function in septic rats

Abstract

Objective To investigates the protective effect of mitochondrial division inhibitor, Mdivi-1, on intestinal barrier function in septic rats. Methods A total of 160 SD rats were randomly and equally divided into sham operation group, sepsis group (established by cecal ligation and puncture), conventional treatment group, and Mdivi-1 treatment group. The rats from the conventional treatment group were given lactated Ringer's solution (35 mL/kg) at an infusion rate of 3 mL/h according to the guidelines for sepsis treatment, and those from the Mdivi-1 treatment group were added with intravenous administration of 1 mg/kg Mdivi-1 for resuscitation on the basis of conventional treatment. After 2 h of resuscitation, intestinal barrier function, intestinal expression of zonula occludes-1 (ZO-1), pathological changes in small intestine, serum concentrations of inflammatory cytokines (including TNF-α and IL-1β), mean arterial blood pressure (MAP), survival time and 72-hour survival rate were observed. Intestinal epithelial cells (IECs) were employed to observe the effect of Mdivi-1 on the expression of ZO-1 under the simulation of LPS. Results The septic rats had significantly increased intestinal permeability, D-lactate level and serum concentrations of TNF-α and IL-1β when compared with those of the sham operation group (P 0.05), and mildly improved intestinal villus disturbance when compared with the sepsis group. Mdivi-1 treatment combined with conventional treatment significantly decreased serum concentrations of TNF-α and IL-1β, intestinal permeability, and D-lactate level in comparison with septic rats (P < 0.05), and pathological results showed clear intestinal villus structure and significantly improved inflammatory cell infiltration. The immunohistochemical results of intestinal tissue showed that ruptured tight junction was observed after sepsis, and Mdivi-1 treatment significantly improved the tight junction rupture. At the cellular level, the expression level of ZO-1 between IECs was significantly decreased after LPS stimulation (P < 0.05), and Mdivi-1 treatment increased LPS-induced decrease in ZO-1 expression (P < 0.05). Conclusion Conclusion Mdivi-1 has a protective effect on intestinal barrier function in septic rats, which may be through its regulating ZO-1 expression.

Keywords

• mdivi-1
• sepsis
• intestinal barrier function
• mitochondria