Protective effects of artesunate on septic lung injury in mice via modulation of heme oxygenase-1
10.3760/cma.j.issn.1671-0282.2015.11.009
- VernacularTitle:青蒿琥酯上调血红素氧合酶-1对脓毒症小鼠急性肺损伤的作用研究
- Author:
Tianhui CAO
;
Lei JIANG
;
Kai KANG
;
Dongsheng FEI
;
Shangha PAN
;
Songgen JIN
;
Mingyan ZHAO
- Publication Type:Journal Article
- Keywords:
Artesunate;
Sepsis;
Heme oxgenase-1;
Acute lung injury
- From:
Chinese Journal of Emergency Medicine
2015;24(11):1227-1233
- CountryChina
- Language:Chinese
-
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), IL-6 (pg/mL) (81.53 ± 26.89 vs.898.52 ± 222.78, P ＜ 0.05) in serum was increased, and the lung protein exudation, pulmonary edema (wet/dry weight ratio: 4.27 ± 0.22 vs.6.78 ±0.73, P ＜ 0.05), pulmonary pathology injury (lung injury score: 2.20 ± 0.2 vs.13.25 ± 2.67, P ＜ 0.05) were aggravated by CLP.The HO-1 and Nrf-2 were up-regulated in lung tissue in CLP group compared with the sham group (P ＜ 0.05).After the intervention of AS, the HO-1 and Nrf-2 were further increased (P＜0.05), theTNF-α (pg/mL) (627.45 ±117.03 vs.307.88 ±72.33, P＜0.05), IL-6 (pg/mL) (898.52 ± 222.78 vs.413.47 ± 115.14, P ＜ 0.05) in serum, lung protein exudation, pulmonary edema (wet/dry weight ratio: 6.78 ± 0.73 vs.5.05 ± 0.61, P ＜ 0.05), pulmonary pathology injury (lung injury score: 13.25 ± 2.67 vs.4.95 ± 1.46, P ＜ 0.05) were attenuated compared with the CLP group.However, the protective role of AS in the septic lung injury in mice was partly reversed by ZnPP, and no significant difference was detected between the AS + CLP + ZnPP and CLP group (lung injury score: 12.15 ± 2.95 vs.13.25 ± 2.67, 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.
