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异甘草素通过增强BKCa电流舒张自发性高血压大鼠脑基底动脉：可溶性鸟苷酸环化酶/环磷酸鸟苷的作用

田伟伟, 赵磊, 马克涛, 李丽, 司军强^*

石河子大学医学院生理学教研室/新疆地方与民族高发病教育部重点实验室，石河子 832002

摘要

本文旨在研究异甘草素(isoliquiritigenin, ISL)对自发性高血压大鼠(spontaneously hypertensive rat, SHR)脑基底动脉的影响。在给予ISL干预前后，用尾动脉测压仪观察收缩压的变化，分离和制备脑基底动脉血管段，对SHR脑基底动脉依次给予1 × 10−5 mol/L苯肾上腺素(phenylephrine, PE)、1 × 10−5 mol/L PE + 1 × 10−4 mol/L ISL和1 × 10−5 mol/L PE灌流后，用压力型小动脉仪测量脑基底动脉的直径，制备SHR脑基底动脉单个血管平滑肌细胞，用全细胞膜片钳记录技术观察大电导钙激活钾通道(large-conductance calcium-activated potassium channels, BKCa)电流的变化，并用ELISA技术检测SHR脑基底动脉内cGMP水平的变化。结果表明：给予ISL干预14天后，SHR收缩压由(218.3 ± 1.6) mmHg降低至(119.2 ± 1.9) mmHg (P < 0.01, n = 6)，与Wistar-Kyoto (WKY)大鼠相比没有显著差异；1 × 10−4 mol/L ISL舒张SHR脑基底动脉(P < 0.01, n = 6)；ISL可显著增加SHR脑基底动脉平滑肌细胞外向电流密度(P < 0.01, n = 6)，该增强作用可被1 × 10−3 mol/L四乙胺(BKCa通道阻断剂)所阻断，而3 × 10−4 mol/L 4-氨基吡啶(Kv通道阻断剂)对ISL增强的平滑肌细胞外向电流密度无明显影响；1 × 10−5 mol/L亚甲蓝(可溶性鸟苷酸环化酶阻断剂)可以抑制ISL增强的平滑肌细胞外向电流密度(P < 0.05, n = 6)；ISL可明显增加SHR脑基底动脉内cGMP水平(P < 0.05, n = 6)。以上结果提示：ISL可能通过增加脑基底动脉平滑肌细胞cGMP含量，增强BKCa通道介导的外向电流，从而发挥舒张SHR脑基底动脉的作用。

关键词： 异甘草素; 脑基底动脉; 大电导钙激活钾通道; 环磷酸鸟苷

分类号：R3

[Isoliquiritigenin relaxes the cerebral basilar artery by enhancing BKCa current in spontaneously hypertensive rat: role of sGC/cGMP .] [Article in Chinese]

TIAN Wei-Wei, Zhao Lei, MA Ke-Tao, LI Li, SI Jun-Qiang^*

Department of Physiology and Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Shihezi 832002, China

Abstract

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10−5 mol/L phenylephrine (PE), 1 × 10−5 mol/L PE + 1 × 10−4 mol/L ISL and 1 × 10−5 mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10−4 mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10−3 mol/L TEA (a BKCa channel inhibitor), but 3 × 10−4 mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10−5 mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.

Key words: isoliquiritigenin; basilar artery; BKCa channel; cGMP

收稿日期：2014-12-09　　录用日期：2015-01-23

通讯作者：司军强　　E-mail: sijunqiang@shzu.edu.cn

引用本文：

田伟伟, 赵磊, 马克涛, 李丽, 司军强. 异甘草素通过增强BKCa电流舒张自发性高血压大鼠脑基底动脉：可溶性鸟苷酸环化酶/环磷酸鸟苷的作用[J]. 生理学报 2015; 67 (3): 329-334.

TIAN Wei-Wei, Zhao Lei, MA Ke-Tao, LI Li, SI Jun-Qiang. [Isoliquiritigenin relaxes the cerebral basilar artery by enhancing BKCa current in spontaneously hypertensive rat: role of sGC/cGMP .] [Article in Chinese]. Acta Physiol Sin 2015; 67 (3): 329-334 (in Chinese with English abstract).