Protective effects of parthenolide on intestinal barrier function in septic rats

Abstract

Objective To investigate the protective effects of parthenolide (PTL) on intestinal barrier function in septic rats. Methods The septic model of rats was established by cecal ligation and puncture (CLP), and SD rats (200±20 g, male/female) were randomly divided into 6 groups: normal control (NC) group, sepsis (Sep) group, conventional treatment (LR) group (lactated Ringer's solution resuscitation+dopamine+cefuroxime sodium), and parthenolide (PTL) groups (1, 5 and 10 mg/kg parthenolide respectively on the basis of LR group). The changes of arterial blood pressure, survival rate and survival time of rats in each group were observed, and the optimal concentration of parthenolide in the treatment was determined. Moreover, the effects of parthenolide (at the optimal concentration) on the intestinal permeability, intestinal pathology, inflammatory cytokine levels, as well as liver and kidney functions in septic rats were further investigated. Results As compared with the NC group, the survival rate and survival time of septic rats were significantly decreased, so was the mean arterial pressure (MAP), while the levels of blood inflammatory cytokines were increased, and the liver and kidney functions were damaged. Conventional treatment improved the survival rate and survival time of septic rats to a certain extent, reduced the levels of inflammation cytokines and alleviated the liver and kidney damages. When compared with the LR group, the survival rates of 1, 5, and 10 mg/kg PTL groups were increased by 6.3%, 43.8%, and 18.8%, respectively, and the MAP in the PTL groups was elevated by 1.4%, 12.8%, and 7.1%, respectively, with those of 5 mg/kg PTL more significant. Further research found that PTL remarkably ameliorated the intestinal barrier function in septic rats, shown as a 55.1% reduction in the content of intestinal Evans blue (EB), a 69.5% decline in blood D-lactic acid concentration as compared with the LR group (P < 0.05), along with an improvement in intestinal epithelial structure, and a decrease in epithelial cell necrosis. In addition, PTL reduced the inflammatory cytokine levels greatly and improved the liver and kidney functions in septic rats. Conclusion PTL shows obvious protective effects on the intestinal barrier function of septic rats, and its mechanism may be related to the inhibition of septic inflammatory response.

Keywords

• parthenolide
• sepsis
• intestinal permeability
• blood inflammatory cytokine