Effects of metformin on mitochondrial oxidative stress in lung tissue of rats with acute lung injury induced by sepsis

Zhang Meng-li; Li Wen-qiang

doi:10.3969/j.issn.1002-1949.2017.11.002

Abstract：Objective To observe the effect of metformin on mitochondrial oxidative stress in lung tissue of rats with acute lung injury induced by sepsis.Methods The rat model of sepsis was established by cecal ligation and perforation (CLP).Forty male Wistar rats were randomly divided into four groups:normal control group (Sham group),control group (Sham/M group),sepsis group (CLP group),sepsis treatment group (CLP/M group).Each group was divided into 6 h,12 h,24 h subgroups according to observation time points.Sham/M group was injected with metformin (100 mg/kg) and the same group as Sham group 1.5 h before operation.The sham rats underwent surgery,but without ligation and puncture.CLP/M group was injected with metformin (100 mg/kg) by intragastric administration 1.5 h before operation.The levels of TNF-α and IL-1 β in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA).The activity of mitochondrial superoxide dismutase (SOD) was measured by xanthine oxidase method.The expression of AMPK protein was detected by protein immunoblotting test (Western blotting).The pathological changes of lung tissue were observed by HE staining.Results ①There were no significant differences in TNF-α and IL-1β levels between the Sham group and the Sham/M group at 12 h and 24 h (P ＞0.05).At 12 h and 24 h,the CLP group and the CLP/M group were significantly (P ＜ 0.01).The levels of TNF-α and IL-1β in lung tissue of CIP/M group were significantly lower than those in CLP group (P ＜ 0.01),and the level of TNF-α and IL-1β in lung tissue of CLP (P ＜ 0.05).②The levels of SOD in the mitochondria of Sham group and Sham/M group were significantly lower than those in Sham group (P ＜ 0.01),CLP/M (P ＜ 0.05).③The expression of AMPK protein in Sham group and Sham/M group was not significantly different (P ＞ 0.05),CLP/M and CLP group were higher than Sham group (P ＜ 0.05);CLP/M group was significantly higher than CLP group (P ＜ 0.05).④The pathological morphology and ultrastructural injury of CLP group were heavier under light microscope.After treatment with metformin,the pathological morphology and ultrasonography microstructure damage has been reduced.Conclusion Metformin may protect the acute lung injury induced by sepsis,which may be related to the decrease of TNF-α and IL-1β inflammatory mediators,the increase of SOD level and the activation of AMPK protein.