Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

Liu

et al. 2022

Pharmaceutical Biology

Context Jingchuan tablet (JCT) is a Chinese medicine prescription for treating ischaemic cerebral stroke (ICS). However, its relevant mechanisms remain unclear. Objective To unravel the intrinsic mechanisms of JCT anti-ICS. Materials and methods ‘Hongjingtian’, ‘chuanxiong’, ‘yanhusuo’, ‘bingpian’, ‘cerebral infarction’, ‘cerebral ischemia’ or ‘stroke’ were used as keywords, and then components, targets and underlying mechanisms of JCT anti-ICS were analysed in TCMSP, TTD, DrugBank, STRING and Metascape databases up to June 2020. Male Sprague-Dawley rats under permanent middle cerebral artery occlusion (pMCAO) model, randomly assigned as: model, sham, nimodipine (0.012 g/kg/d) and JCT (0.78, 1.56 and 3.12 g/kg/d) groups, received oral gavage administration for a week. Therapeutic effects were evaluated by detecting the proportion of cerebral infarction, neuronal apoptosis and neurological deficits. Bioactive components were detected by HPLC–MS. Molecular biology and computational docking were used to verify the underlying mechanisms. Results Eighty-one components, 166 targets and HIF-1α/EPO/VEGFA pathway contributed to the anti-ICS effect of JCT. JCT treatment effectively reduced the proportion of cerebral infarction (33.13%), apoptosis rate (14.80%) and neurobehavioural score (2.00). JCT increased the protein levels of HIF-1α (0.84), EPO (0.64) and VEGFA (0.69), respectively ( p < 0.05). Gallic acid, salidroside, chlorogenic acid, ethyl gallate, ferulic acid and tetrahydropalmatine detected by HPLC–MS showed good interaction and binding with HIF-1α/EPO/VEGFA. Conclusions Our study demonstrated the mechanisms of JCT anti-ICS associated with the activation of the HIF-1α/EPO/VEGFA pathway, which provided a pharmacological basis for expanding the clinical application and some scientific ideas for further research into the material basis JCT anti-ICS.

Section: Discussionmentioning

confidence: 99%

The therapeutic role of Jingchuan tablet on ischaemic cerebral stroke via the HIF-1α/EPO/VEGFA signalling pathway

Liu

et al. 2022

Pharmaceutical Biology

J of Oral Rehabilitation

“…Then, 3D reconstruction by the manufacturer was conducted, and the retropalatal space in the UA was examined from the top, 1/4, 1/2 and 3/4 levels to the bottom of the soft palate. 15 PSG (Rembrandt Embla Polysomnography System, Reykjavik, Iceland) was used to monitor the sleep parameters. PSG recordings were conducted as described in our previous studies.…”

Section: Confirmation Of Induced Osahsmentioning

confidence: 99%

A mandibular advancement device attenuates the abnormal morphology and function of mitochondria from the genioglossus in obstructive sleep apnea–hypopnea syndrome rabbits

Liu,

Zhang,

Zhu

et al. 2024

Self Cite

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) is a serious and potentially life‐threatening disease. Mandibular advancement device (MAD) has the characteristics of non‐invasive, comfortable, portable and low‐cost, making it the preferred treatment for mild‐to‐moderate OSAHS. Our previous studies found that abnormal contractility and fibre type distribution of the genioglossus could be caused by OSAHS. However, whether the mitochondria participate in these tissue changes is unclear. The effect of MAD treatment on the mitochondria of the genioglossus in OSAHS is also uncertain.ObjectiveTo examine the morphology and function of mitochondria from the genioglossus in a rabbit model of obstructive sleep apnea–hypopnea syndrome (OSAHS), as well as these factors after insertion of a mandibular advancement device (MAD).MethodsThirty male New Zealand white rabbits were randomised into three groups: control, OSAHS and MAD, with 10 rabbits in each group. Animals in Group OSAHS and Group MAD were induced to develop OSAHS by injection of gel into the submucosal muscular layer of the soft palate. The rabbits in Group MAD were fitted with a MAD. The animals in the control group were not treated. Further, polysomnography (PSG) and cone‐beam computed tomography (CBCT) scan were used to measure MAD effectiveness. CBCT of the upper airway and PSG suggested that MAD was effective. Rabbits in the three groups were induced to sleep for 4–6 h per day for eight consecutive weeks. The genioglossus was harvested and detected by optical microscopy and transmission electron microscopy. The mitochondrial membrane potential was determined by laser confocal microscopy and flow cytometry. Mitochondrial complex I and IV activities were detected by mitochondrial complex assay kits.ResultsOSAHS‐like symptoms were induced successfully in Group OSAHS and rescued by MAD treatment. The relative values of the mitochondrial membrane potential, mitochondrial complex I activity and complex IV activity were significantly lower in Group OSAHS than in the control group; however, there was no significant difference between Group MAD and the control group. The OSAHS‐induced injury and the dysfunctional mitochondria of the genioglossus muscle were reduced by MAD treatment.ConclusionDamaged mitochondrial structure and function were induced by OSAHS and could be attenuated by MAD treatment.

“…It is a feasible idea to establish an OSA animal model by injecting dilatants (such as polytetrafluoroethylene and hydrophilic polyacrylamide gel) into soft tissues of the upper airway, such as the tongue or the soft palate, which can cause persistent swelling and narrowing of the upper airway soft tissues (32)(33)(34)(35)(36)(37). Polytetrafluoroethylene (PTFE) is an inert swelling agent used in the treatment of vesicoureteral reflux.…”

Section: Spontaneous Upper Airway Narrowing Modelmentioning

confidence: 99%

Advances in animal models of obstructive sleep apnea

Zong

Du²,

Li³

et al. 2023

Front. Med.

Animal experiments play an important role in the study of the pathogenesis of human diseases and new methods of diagnosis and treatment. Due to the great differences in the anatomical structure and physiology of the upper airway between animals and humans, there is currently no animal model that can fully simulate the pathological anatomy and pathophysiological characteristics of human obstructive sleep apnea (OSA) patients. Herein, we summarizes the construction methods of several OSA animal models that have been widely used in the studies published in the last 5 years, the advantages and limitations of each model as well as related evaluation techniques are described. This information has potential to provide further guide for the development of OSA related animal experiments.