Down-Regulation of Mir-21 Alleviates Lung Injury Induced by Burns Through Activating Silent Mating Type Information Regulation 2 Homolog 1 (SIRT1)-Protein Kinase B (AKT)-Nuclear Factor κB (NF- κB) Pathway

Abstract

Severe burns can cause lung damage. Mir-21 is a promising biomarker for inflammatory response. However, the expression and role of Mir-21 in lung injury have not been elucidated. SD rats were divided into control group; model group; Mir-21 inhibition group; Mir-21 inhibition + SIRT1 inhibitor (nicotinamide) group followed by analysis of Mir-21 expression by real time PCR, arterial blood gas index and lung wet-to-dry weight ratio, lung tissue MPO and SOD activities, protein content and cell count in bronchoalveolar lavage fluid, secretion of TNF-α and IL-2 by ELISA, SIRT1 expression by Real time PCR and ELISA and Akt and NF-κB level by Western blot. Compared with control group, model group showed significantly decreased PaO2 and pH, increased W/D and MPO activity increased, decreased SOD activity, increased protein content and cell count in BALF, Mir-21 expression, and secretion of TNF-α and IL-2, decreased SIRT1 expression, and promoted pAkt and NF-κB expression (P < 0 05). Down-regulation of Mir-21 significantly improved blood gas index, decreased W/D and MPO activity, increased SOD activity, decreased TNF-α and IL-2 secretion; increased SIRT1 expression, and decreased pAkt and NF-κB expression (P < 0 05). However, SIRT1 inhibitor significantly reversed the effect of down-regulation of Mir-21 on the protection of lung injury. Downregulation of Mir-21 regulates SIRT1-Akt-NFκB pathway and oxidative stress, reduces inflammation, and thus alleviates burn-induced lung injury, and may be a new option for treating acute lung injury.