Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy

摘要

Background & aims: Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. Methods: 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. Results: The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% (. p < 0.01), reduced immune cell infiltration 21 ± 6% (H&E) and 42 ± 8% (CD45 immunohistochemistry (. p < 0.05)), reduced macrophage infiltration 48 ± 10% (F4/80 immunohistochemistry (. p < 0.05)), and increased IL-6, PGC-1α, and utrophin mRNA 247 ± 77%, 27 ± 17%, and 43 ± 23% respectively (. p ≤ 0.05). Utrophin, Sirt1, and PGC-1α protein expression did not change. Conclusions: Resveratrol may be a therapy for DMD by reducing inflammation.