Trichostatin A reverses rocuronium resistance in burn-injured rats.

Abstract

This study aimed to investigate whether the histone deacetylase HDAC4 inhibitor, trichostatin A (TSA), could reverse resistance to non-depolarizing muscle relaxants (NDMRs) caused by burn injuries. A rat burn injury model was established, in which TSA was administered to inhibit HDAC4 expression. The potency of rocuronium was assessed through tension tests, and the levels of HDAC4 and myogenin proteins were determined using Western blot. Additionally, siRNA was utilized to explore the effects of HDAC4 knockdown on rocuronium potency and protein expression. The burn injuries increased the IC₅₀ of rocuronium, which was reversed by TSA treatment. Furthermore, HDAC4 and myogenin protein expression levels were increased significantly in burned legs, a phenomenon that TSA effectively counteracted. HDAC4 knockdown decreased rocuronium IC₅₀ and lowered HDAC4 and myogenin protein expression in the subsequent burn injuries. The HDAC4 inhibitor TSA has the ability to mitigate NDMR resistance in skeletal muscle via the HDAC4-myogenin pathway after burn injuries.