Effects of triptolide and methotrexate nanosuspensions on left ventricular remodeling in autoimmune myocarditis rats

Int J Nanomedicine. 2019 Jan 29:14:851-863. doi: 10.2147/IJN.S191267. eCollection 2019.

Abstract

Purpose: This study was carried out to investigate the effects of a triptolide (TP) nanosuspension and methotrexate (MTX) nanosuspension on left ventricular remodeling and cardiac function for autoimmune myocarditis (EAM) in rats. The regulating effects on inflammatory cytokines in the peripheral serum and related mechanisms are also discussed.

Methods: First, TP and MTX were prepared as a nanosuspension, and the EAM model was successfully established in rats with cardiac myosin. Then, the effect of TP and MTX suspensions was tested in an EAM model.

Results: Results revealed that both TP and MTX suspensions could reduce the degree of myocardial fibrosis and delay the remodeling process of the left ventricle which could further improve cardiac function. Finally, it was found that inflammatory cytokines in the peripheral serum were regulated by the nonspecific immune system and the inhibition of nuclear factor-κB signaling might have partly occurred due to this mechanism.

Conclusion: In summary, this study provided a complete foundation for EAM therapy of profound clinical relevance.

Keywords: dilated cardiomyopathy; heart failure; immunoregulation; inflammatory cytokines; suspension.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Collagen / metabolism
  • Cytokines / blood
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Epoxy Compounds / pharmacology
  • Epoxy Compounds / therapeutic use
  • Heart Function Tests
  • Heart Ventricles / drug effects
  • Heart Ventricles / pathology
  • Male
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use*
  • Myocarditis / blood
  • Myocarditis / diagnostic imaging
  • Myocarditis / drug therapy*
  • Myocarditis / physiopathology*
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B / metabolism
  • Nanoparticles / chemistry*
  • Organ Size / drug effects
  • Particle Size
  • Phenanthrenes / pharmacology
  • Phenanthrenes / therapeutic use*
  • Phosphorylation / drug effects
  • Rats, Inbred Lew
  • Signal Transduction / drug effects
  • Suspensions
  • Ventricular Remodeling / drug effects*

Substances

  • Cytokines
  • Diterpenes
  • Epoxy Compounds
  • NF-kappa B
  • Phenanthrenes
  • Suspensions
  • triptolide
  • Collagen
  • Methotrexate