Protective effects of artesunate on septic lung injury in mice via modulation of heme oxygenase-1

Abstract

Objective To investigate the effects of artesunate (AS) on septic lung injury in mice and to study the modulation of heme oxygenase-1 (HO-1) in lung in order to clarify the mechanism of AS action. Methods Sixty male Kunming mice were randomly (random number) divided into four groups: Sham group ( n =15 ) , CLP group ( n =15) , AS+CLP group ( n =15) and AS+ZnPP+CLP group ( n =15). Cecal ligation and puncture (CLP) method was employed to induce septic lung injury. AS (15 mg/kg) was injected into the abdomen of mice 2 hours before the CLP procedures, and ZnPP IX, an inhibitor of HO-1, was intraperitoneally injected in dose of 40 μmol/kg 1 hour after the AS injection. The equivalent volume of normal saline was intraperitoneally injected instead in mice of Sham group and CLP group. The mice were sacrificed 24 hours after the CLP procedures. The TNF-α, IL-6 in serum were assayed by ELISA method. The lung injury score and wet/dry ratio were measured. The western blotting and immunohistochemistry methods were used to determine HO-1 protein expression in lung tissue. The protein level of nuclear factor-E2-related factor-2 (Nrf-2) , an important transcriptional factor of HO-1 in lung tissue was also analyzed by western blotting. One-way analysis of variance (ANOVA) was used for comparisons among the groups, and SNK-q (Student-Newman-Keuls) test was performed for further comparison, and difference was statistically significant at P <0.05. Results The TNF-α (pg/mL) (54.37 ± 15.59 vs. 627.45±117.03, P 0.05; wet/dry weight ratio: 6.78 ± 0.73 vs. 6.29±0.82, P >0.05). Conclusions AS plays protective roles in septic lung injury, and it is attributed to limiting lung inflammation via up-regulation of HO-1. Key words: Artesunate; Sepsis; Heme oxgenase-1; Acute lung injury