Abstract
The protective functions of thalidomide in paraquat (PQ)-induced injury have been reported. But the mechanisms remain largely unknown. In this research, a PQ-treated rat model was established and further treated with thalidomide. Oedema and pathological changes, oxidative stress, inflammation, fibrosis and cell apoptosis in rat lungs were detected. A PQ-treated RLE-6TN cell model was constructed, and the viability and apoptosis rate of cells were measured. Differentially expressed microRNAs (miRNAs) after thalidomide administration were screened out. Binding relationship between miR-141 and histone deacetylase 6 (HDAC6) was validated. Altered expression of miR-141 and HDAC6 was introduced to identify their involvements in thalidomide-mediated events. Consequently, thalidomide administration alone exerted no damage to rat lungs; in addition it reduced PQ-induced oedema. The oxidative stress, inflammation and cell apoptosis in rat lungs were reduced by thalidomide. In RLE-6TN cells, thalidomide increased cell viability and decreased apoptosis. miR-141 was responsible for thalidomide-mediated protective events by targeting HDAC6. Overexpression of HDAC6 blocked the protection of thalidomide against PQ-induced injury via activating the IkBα-NF-κB signalling pathway. Collectively, this study evidenced that thalidomide protects lung tissues from PQ-induced injury through a miR-141/HDAC6/IkBα-NF-κB axis.