Department of Cardiovascular Surgery, Faculty of Medicine, University of Adiyaman, Adiyaman, 02040, Turkey.
Department of Pharmacology, Faculty of Medicine, University of Adiyaman, Adiyaman, 02040, Turkey.
Curr Med Sci. 2021 Apr;41(2):381-389. doi: 10.1007/s11596-021-2358-6. Epub 2021 Apr 20.
The aim of the current study was to investigate the pharmacological activity of glabridin on the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placed in Krebs solution at +4°C and hung in an isolated organ bath to assess their contraction/relaxation responses. The contraction/relaxation responses were recorded to observe if the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridin after treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor), isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant, a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, and PKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(ω)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX, and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of human SV pretreated with PE in a dose-dependent manner, which was independent of the endothelium. The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823. Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NO level. The enhancing effects of cGMP and PKG levels by glabridin were abolished by ODQ and KT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activation of BK channels and inhibition of PDE.
本研究旨在探讨甘草素对离体人隐静脉（SV）的药理学活性，并探讨其潜在机制。在旁路手术中切除患者 SV 样本，将 4mm 长的血管置于 +4°C 的 Krebs 溶液中，并悬挂在离体器官浴中，以评估其收缩/松弛反应。记录收缩/松弛反应，观察环鸟苷单磷酸（cGMP）/蛋白激酶 G（PKG）通路是否介导甘草素在使用 ODQ（鸟苷酸环化酶抑制剂）、KT5823（PKG 抑制剂）、异丁基甲基黄嘌呤[IBMX，磷酸二酯酶（PDE）抑制剂]和斑蝥素[Cant，肌球蛋白轻链磷酸酶（MLCP）抑制剂]等阻滞剂治疗后的松弛作用。此外，在用甘草素孵育后，通过 ELISA 测定 SV 组织中的一氧化氮（NO）、cGMP 和 PKG 水平，以及用 N（ω）-硝基-L-精氨酸甲酯（L-Name，NO 合酶抑制剂）、苯肾上腺素（PE）、ODQ、IBMX 和 KT5823 孵育后。结果表明，甘草素以剂量依赖的方式松弛 PE 预处理的人 SV 血管平滑肌，这与内皮无关。甘草素的血管舒张作用仅被 Iberiotoxin（IbTX）、Cant 和 KT5823 抑制。甘草素增加 SV 匀浆中的 cGMP 和 PKG 水平，但不改变 NO 水平。ODQ 和 KT5823 可消除甘草素对 cGMP 和 PKG 水平的增强作用。总之，甘草素有血管舒张作用，这与其激活 BK 通道和抑制 PDE 有关。
