Table 2.
Basic research on drugs for the treatment of OSA-related AS.
| Drug name | Research subjects | Hypoxic conditions in the experimental group | Intervention period (weeks) | Experimental dose | Mechanism of action |
|---|---|---|---|---|---|
| DHA [148] | Male ApoE−/− mice | 5–21% FiO2, 60 s/cycle, 8 h/d | 8 | Dietary intake of 0.5% fish oil (containing 80% DHA/4% eicosapentaenoic acid) | AA↓, MMP-2 expression↓ → AS↓ |
| Mirabegron [156] | Male ApoE−/− mice | 5–21% FiO2, 60 s/cycle, 8 h/d | 6 | 10 mg/kg/d | Nitrotyrosine↓, dihydroglutaraldehyde↓, SOD↑, GSH↑ → OS↓ → AS↓ |
| Atorvastatin [158, 163] | Male C57BL/6 mice | 6–21% FiO2, 60 s/cycle, 8 h/d | 12 | 5 mg/kg/d | OS↓ → AS↓ |
| Male Wistar rats | 5–21% FiO2, 60 s/cycle, 8 h/d | Simultaneous protocol for 2 weeks Delayed protocol for 4 weeks |
10 mg/kg/d | ||
| Chinese medicine [162] | Male ApoE−/− mice | (10 ± 0.5%)–(21 ± 0.5%) FiO2, 180 s/cycle, 8 h/d | 8 | Medium dose: 1500 mg Zhenyuan capsule +500 mg ligustrazine phosphate tablet. The high-dose and low-dose groups were administered 2 times and 1/2 of the medium dose, respectively. | LDL-C↓, TNF-α↓, HIF-1α↓, SREBP-1c↓, FAS↓; SOD↑, HDL-C↑ → blood lipid↓, inflammation↓, OS↓ → AS↓ |
| Montelukast [164] | Male ApoE−/− mice | 21–5% FiO2, 60 s/cycle, 8 h/d | 8 | 1 mg/kg/d | CysLT 1 receptor blocking → vascular remodeling↓ → AS↓ |
| DMB [165] | Male Ldlr−/− mice; male ApoE−/− mice | 21–8% FiO2, 0.5–8% CO2, 8 min/cycle, 10 h/d | 8 | 1.0%, vol/vol | TMA↓ → TMAO↓ → inflammation, dyslipidemia↓ → AS↓ |
| Propofol [161] | Human endothelial cell line EA.hy926 cells | 1% O2 10 min+21% O2 5 min, 15 min/cycle | 64 cycles | 0, 25, 50, and 100 μM (four concentrations) |
p38 MAPK↓ → NF-κB↓, IL-6↓, TNF↓, IL-1β↓ → inflammation↓ → AS↓ |
| Salidroside [166] | Male ApoE−/− mice; HUVECs | Hypoxic conditions for mice: 21%–5%–21% FiO2, 120 s/cycle, 12 h/d Hypoxic conditions for HUVECs: 21%–5%–21%, 40 min/cycle |
7 weeks for mice; 72 cycles for HUVECs | Mice: 100 mg/kg/d; HUVECs: 10 or 100 μM | cAMP/PKA↑ → RhoA/ROCK↓ → ROS↓ → endothelial barrier function↑ → AS↓ |
GSH: glutathione; SOD: superoxide dismutase; FiO2: fraction of inspiration oxygen; AA: arachidonic acid; MMP-2: matrix metalloproteinase 2; DHA: docosahexaenoic acid; SREBP: sterol-regulatory element-binding protein; FAS: a downstream molecule of SREBP-1c; SOD: superoxide dismutase; HDL-C: high-density lipoprotein cholesterol; IHR: intermittent hypoxia/reoxygenation; HUVECs: human umbilical vein endothelial cells; ROS: reactive oxygen species; RhoA: ras homolog gene family member A; ROCK: rho-associated protein kinase; PKA: protein kinase A; CysLT: cysteinyl leukotriene; DMB: 3,3-dimethyl-1-butanol; ApoE−/−, apolipoprotein E deficient; Ldlr−/−: low-density lipoprotein receptor deficient; IHC: intermittent hypoxia and hypercapnia; RA: room air; HFD: high-fat diet; TMA: trimethylamine; TMAO: trimethylamine N-oxide.