Therapeutic effects and modulatory mechanism of Alpiniae oxyphyllae Fructus in chronic intermittent hypoxia induced enuresis in rats

Sleep Breath. 2020 Mar;24(1):329-337. doi: 10.1007/s11325-019-01983-4. Epub 2020 Jan 2.

Abstract

Objective: The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)-induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE).

Methods: Female rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3-adrenergic receptor (ß3-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group.

Results: Compared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P2X3 receptor and muscarinic M3 receptor were expressed at higher levels, and ß3-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P2X3 receptor and muscarinic M3 receptor and increased the expression of the ß3-AR.

Conclusions: AOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P2X3 receptor, muscarinic M3 receptor, and ß3 adrenergic receptor.

Keywords: Alpiniae oxyphyllae Fructus; Bladder receptor; Chronic intermittent hypoxia; Enuresis; Oxidative stress.

MeSH terms

  • Alpinia
  • Animals
  • Disease Models, Animal*
  • Enuresis / blood
  • Enuresis / prevention & control*
  • Female
  • Hypoxia / blood
  • Hypoxia / complications*
  • Malondialdehyde / blood
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Rats
  • Receptor, Muscarinic M3 / drug effects
  • Receptors, Adrenergic, beta-3 / drug effects
  • Receptors, Purinergic P2X3 / drug effects
  • Superoxide Dismutase / blood
  • Urinary Bladder / drug effects
  • Urination / drug effects

Substances

  • Alpinia oxyphylla fruit extract
  • Plant Extracts
  • Receptor, Muscarinic M3
  • Receptors, Adrenergic, beta-3
  • Receptors, Purinergic P2X3
  • Malondialdehyde
  • Superoxide Dismutase