Department of Cardiology, Shanghai Tenth Clinical Medical School of Nanjing Medical University, Shanghai, China (mainland).
Department of Cardiology, The Sixth People's Hospital South Campus affiliated with Shanghai Jiaotong University, Shanghai, China (mainland).
Med Sci Monit. 2018 Jan 12;24:246-253. doi: 10.12659/msm.907745.
BACKGROUND Diosgenin, a phytosteroid sapogenin, has anti-inflammatory properties shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the specific mechanism by which this is achieved is not clear. This study investigated the protective effects of diosgenin on myocardial ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms. MATERIAL AND METHODS Healthy adult male SD rats, body weight (b.w.) 250-280 g, were used to model ischemia-reperfusion injury (IRI) and were administered diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks before surgery. The left anterior descending artery (LAD) was ligated to induce myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min while relevant indicators were detected. RESULTS Both 50 mg and 100 mg diosgenin oral administration increased left ventricular developed pressure (LVDP) and maximum changing rate of ventricular pressure (±dp/dtmax), decreased left ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC staining suggested that diosgenin reduced myocardial infarct size in the rat model. Pathological results showed that myocardial ischemia and inflammation were alleviated by diosgenin. In addition, the increased expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) in serum, and myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin administration. Diosgenin further inhibited the phosphorylation of transcription factor NF-κB and modulated the expression of downstream inflammatory cytokines by regulating the activation of p38-MAPK and JNK pathways. CONCLUSIONS Results demonstrate diosgenin plays an anti-inflammatory role in the protection of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF-κB.
薯蓣皂苷元是一种植物甾醇皂苷元,具有抗炎特性,可减轻心肌缺血再灌注损伤(MIRI)。然而,其具体作用机制尚不清楚。本研究旨在探讨薯蓣皂苷元对心肌缺血/再灌注(I/R)的保护作用及其潜在的抗炎机制。
健康成年雄性 SD 大鼠,体重 250-280 g,用于构建缺血再灌注损伤(IRI)模型,并在术前连续 4 周每天给予薯蓣皂苷元(50 mg/kg 和 100 mg/kg b.w.)灌胃。结扎左前降支(LAD)诱导心肌缺血 30 min 后再灌注 30 min、60 min 和 120 min,同时检测相关指标。
薯蓣皂苷元(50 mg 和 100 mg)口服给药均增加左心室发展压(LVDP)和心室压力最大变化率(±dp/dtmax),降低左心室舒张末期压(LVEDP)和心肌酶标志物。TTC 染色表明薯蓣皂苷元减少了大鼠模型的心肌梗死面积。病理结果显示薯蓣皂苷元减轻了心肌缺血和炎症。此外,薯蓣皂苷元给药显著抑制了血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的表达以及心肌髓过氧化物酶(MPO)的增加。薯蓣皂苷元通过调节 p38-MAPK 和 JNK 通路的激活,进一步抑制转录因子 NF-κB 的磷酸化,并调节下游炎症细胞因子的表达。
结果表明,薯蓣皂苷元通过调节 p38-MAPK 和 JNK 通路以及 NF-κB 的磷酸化在保护 MIRI 中发挥抗炎作用。