ABSTRACT
Objective Metformin (MET) can reduce blood glucose, act against inflammation, lessen oxidative stress and prevent fibrosis. This study was to investigate the protective effect of MET against acute lung injury (ALI) induced by paraquat poisoning (PQP) in rats. Methods Totally 78 healthy adult SPF male SD rats were randomly divided into five groups, normal control, PQP model control, and low-, medium- and high-dose MET. The PQP model was established in the latter four groups of rats by intraperitoneal injection of paraquat solution at 30 mg/kg and, at 2 hours after modeling, the rats in the three MET intervention groups were treated intragastrically with MET at 100, 400 and 800 mg/kg/d respectively, while those in the normal and PQP model control groups with the same amount of normal saline, all for 7 successive days. Six of the animals from each group were sacrificed at 1, 3 and 7 days and their lung tissues harvested for measurement of the wet/dry weight ratio of the pulmonary tissue and contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the plasma, determination of the levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by ELISA, and observation of the pathological changes in the pulmonary tissue by HE staining. Results In the normal control, PQP model control and low-, medium- and high-dose MET groups, the contents of MDA were (2.53±0.36), (3.68±0.26), (3.57±0.52), (3.56±0.83) and (3.68±0.60) nmol/mL respectively on the 1st day of intervention and (2.53±0.36), (5.18±0.56), (5.09±0.88), (3.80±0.91) and (3.96±0.78) nmol/mL at 7 days; those of SOD were (256.18±18.18), (229.24±18.26), (224.65±19.27), (223.20±19.37) and (226.45±11.62) U/mL on the 1st day and (256.18±18.18), (152.06±17.03), (150.76±18.18), (205.95±13.16) and (208.37±12.23) U/mL at 7 days; those of IL-1β were (10.57±2.24), (21.97±5.03), (22.33±4.88), (21.78±5.21) and (22.11±4.19) pg/mL on the 1st day and (10.57±2.24), (91.86±8.40), (91.36±10.65), (63.52±7.06) and (60.35±6.70) pg/mL at 7 days; those of IL-6 were (21.35±2.62), (45.61±3.71), (44.83±5.97), (46.17±7.33) and (45.78±6.55) pg/mL on the 1st day and (21.35±2.62), (84.38±10.21), (85.88±6.70), (49.08±7.70) and (50.26±7.65) pg/mL at 7 days; and those of TNF-α were (32.37±3.74), (71.89±6.98), (72.52±8.23), (71.13±4.50) and (70.15±6.47) pg/mL on the 1st day and (32.37±3.74), (197.04±14.80), (201.59±13.61), (140.17±14.84) and (139.86±11.12) pg/mL at 7 days. Compared with the normal controls, the rats in the PQP model control and the MET intervention groups showed significant increases in the wet/dry weight ratio of the pulmonary tissue and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but a decrease in the SOD level in the plasma at 1, 3 and 7 days (P < 0.05). In comparison with the PQP model controls, the animals in the medium- and high-dose MET groups exhibited remarkable decreases in the wet/dry weight ratio of the lungs and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but an increase in the SOD level at 7 days (P < 0.05). Massive inflammatory cell infiltration, diffuse pulmonary hemorrhage, alveolar collapse and extensive alveolar septal thickening were observed in the PQP model control and low-dose MET groups but significantly alleviated in the medium- and high-dose MET groups at 7 days. Conclusion Metformin can protect paraquat-poisoned rats against acute lung injury by reducing pulmonary edema and the expressions of inflammation- and oxidation-related factors in the pulmonary tissue.