Rapamycin reverses paraquat-induced acute lung injury in a rat model through inhibition of NFκB activation.

OBJECTIVE: To evaluate the role of rapamycin (RAPA) in paraquat (PQ)-induced acute lung injury.

METHODS: Lung tissues were stained with HE and lung histology was observed. Mortality rate, and neutrophil and leukocyte count in blood and bronchoalveolar lavage fluid (BALF) were recorded. Protein content in BALF was determined by Coomassie blue staining. Malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity in blood were determined by thiobarbituric acid (TBA) assay, pyrogallol autoxidation method, and modified Haefman method, respectively. The NF-κB activity was measured by gel electrophoretic mobility shift assay (EMSA). Carbon dioxide partial pressure (PaCO2), partial pressure of oxygen (PaO2) and pH values were measured by automated blood gas analyzer.

RESULTS: HE staining results demonstrated RAPA alleviated pathological changes of acute alveolitis in SD rats. Trend of protein content in BALF was PQ group>RAPA treatment group>control group (P<0.05). Neutrophil and leukocyte count in RAPA treatment group was significantly lower than PQ group at 3, 5, and 7 days after injection (P<0.05). Trend of MDA content was RAPA treatment group>PQ group>control group (P<0.05). Trend of GSH-Px and SOD activity was control group>RAPA treatment group>PQ group (P<0.05). Compared with PQ group, PaO2 in RAPA treatment group was markedly higher and PaCO2 was lower (P<0.05).

CONCLUSION: PQ-induced acute lung injury was effectively reversed with RAPA, through inhibition of NF-κB activation.