Oxymatrine protects cardiac allografts by regulating immunotolerant cells

Int Immunopharmacol. 2021 Nov:100:108080. doi: 10.1016/j.intimp.2021.108080. Epub 2021 Aug 25.

Abstract

Organ transplantation is an effective treatment strategy for patients with irreversible organ failure or congenital organ dysfunction. Oxymatrine (OMT) is a quinolizidine alkaloid with protective and anti-inflammatory effects on tissues and organs. The objective of this study was to investigate whether OMT could exert protective effects in cardiac allografts by regulating immune cells. In vitro cell proliferation and co-culture experiments were used to measure the effects of OMT on splenocyte proliferation and differentiation. In the in vivo study, C57BL/6 mice transplanted with BALB/c cardiac grafts were randomly divided into untreated, low-dose OMT treated, middle-dose OMT treated, high-dose OMT treated, and rapamycin-treated groups. Haematoxylin and eosin and immunohistochemical staining were used to assess pathological changes in the grafts, and fluorescence-activated cell sorting analysis was performed to measure the percentages of immune cells. The results showed that, in the in vitro study, OMT inhibited splenocyte proliferation, decreased the percentage of mature dendritic cells (DCs), and increased the percentage of regulatory T cells (Tregs) and regulatory B cells (Bregs). In the in vivo study, OMT exerted allograft protective effects by prolonging survival time, alleviating pathological damages to the cardiac allograft, decreasing intragraft CD3+ cell and increasing intragraft Foxp3+ cell infiltration, decreasing the percentages of mature DCs, increasing the percentages of Tregs and Bregs, and inhibiting the function of DCs. In conclusion, our study demonstrates that OMT exerted a protective effect on cardiac allografts by regulating immunotolerant cells. More in-depth studies of OMT may provide additional insight into the use of immunosuppressive drugs as a post-transplantation treatment strategy.

Keywords: Acute allograft rejection; Cardiac transplantation; Immunotolerant cell; Mice; Oxymatrine.

MeSH terms

  • Alkaloids / pharmacology*
  • Alkaloids / therapeutic use
  • Allografts / drug effects*
  • Allografts / immunology
  • Allografts / pathology
  • Animals
  • B-Lymphocytes, Regulatory / drug effects
  • B-Lymphocytes, Regulatory / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Heart Transplantation / adverse effects*
  • Humans
  • Immune Tolerance / drug effects
  • Male
  • Mice
  • Quinolizines / pharmacology*
  • Quinolizines / therapeutic use
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Alkaloids
  • Quinolizines
  • oxymatrine