School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1044-1052. doi: 10.1111/1440-1681.13156. Epub 2019 Aug 30.
Isoliquiritigenin (ISL) is a flavonoid substance with a chalcone structure, which exerts anti-tumour, anti-oxidation and anti-inflammatory activity. The large-conductance calcium-activated potassium channel (BK ) is an important potassium channel with negative feedback regulation on the vascular smooth muscle cells (VSMCs) membrane. The activation of BK channel causes the hyperpolarization of VSMCs. It plays an important role in relaxation of blood vessels. Previous studies have shown that ISL causes the relaxation of the aorta and the basilar artery of the rat. However, there have not been studies on regulation of ISL in mesenteric arteries. To examine whether ISL causes the relaxation of the mesenteric artery of mice, we recorded vasodilation of mouse mesenteric arterial rings with a myograph. After contraction of arterial rings with phenylephrine, we added ISL to the arterial rings and measured its relaxation effect. To further examine which channel was involved in this relaxation effect, we tested the effects of ISL on endothelium-dependent and endothelium-independent vasodilation. Then we used BK channel blockers tetraethylammonium and iberiotoxin, to detect whether the BK channel is involved in ISL-induced vasodilation. Mesenteric arterial smooth muscle cells were isolated by enzyme digestion. Bis-(1, 3-dibutylbarbituric acid) trimethine oxonol staining was used to measure membrane potential of mesenteric arterial smooth muscle cells. We identified a vasodilation effect caused by ISL on mouse mesenteric arterial rings pre-contracted by phenylephrine in a concentration-dependent manner, with an EC of 13.71 ± 1.1 μmol/L. The vasodilation effect of ISL is endothelium-independent. K channel inhibitors tetraethylammonium and iberiotoxin reduced the vasodilation induced by ISL which suggested the involvement of BK channel.
甘草素（ISL）是一种具有查尔酮结构的类黄酮物质，具有抗肿瘤、抗氧化和抗炎活性。大电导钙激活钾通道（BK）是一种重要的钾通道，对血管平滑肌细胞（VSMCs）膜具有负反馈调节作用。BK 通道的激活导致 VSMCs 超极化，在血管舒张中起重要作用。先前的研究表明，ISL 可引起大鼠主动脉和基底动脉舒张。然而，关于 ISL 对肠系膜动脉的调节作用尚未有研究。为了研究 ISL 是否引起小鼠肠系膜动脉舒张，我们使用肌动描记器记录小鼠肠系膜动脉环的血管舒张。在血管环用苯肾上腺素收缩后，我们向血管环中加入 ISL，并测量其舒张作用。为了进一步研究哪种通道参与这种舒张作用，我们测试了 ISL 对内皮依赖性和非内皮依赖性血管舒张的作用。然后，我们使用 BK 通道阻断剂四乙铵和 Iberiotoxin，检测 BK 通道是否参与 ISL 诱导的血管舒张。通过酶消化分离肠系膜动脉平滑肌细胞。使用双（1,3-二丁基巴比妥酸）三甲氧基氧杂吖啶染色测量肠系膜动脉平滑肌细胞的膜电位。我们确定了 ISL 对预先用苯肾上腺素收缩的小鼠肠系膜动脉环的血管舒张作用呈浓度依赖性，EC 为 13.71±1.1μmol/L。ISL 的血管舒张作用是内皮非依赖性的。K 通道抑制剂四乙铵和 Iberiotoxin 降低了 ISL 诱导的血管舒张作用，表明 BK 通道的参与。
