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18β-甘草次酸抑制微动脉平滑肌细胞外向电流

马克涛, 李新芝, 李丽, 张忠双, 石文艳, 司军强^*

石河子大学医学院 新疆地方与民族高发病教育部重点实验室电生理研究室；生理学教研室，石河子 832002

摘要

本文旨在观察18β-甘草次酸(18β-glycyrrhetinic acid, 18βGA)对微动脉平滑肌细胞膜电流的影响。分离出豚鼠小脑前下动脉(anterior inferior cerebellar artery, AICA)和肠系膜动脉(mesenteric artery, MA)后，用酶消化法制备单个血管平滑肌细胞(vascular smooth muscle cells, VSMCs)，应用全细胞膜片钳技术记录平滑肌细胞外向电流的变化。结果显示：(1) 1 mmol/L 4-氨基吡啶(4-aminopyridine, 4-AP)和1 mmol/L tetraethylammonium (TEA)都可以部分抑制微动脉平滑肌细胞的外向电流。(2)18βGA电压和浓度依赖性地抑制微动脉平滑肌细胞外向电流。18βGA主要抑制0~+40 mV电压区间的激活电流，其中对+40 mV激活电流的抑制作用最强。10、30和100 µmol/L 18βGA对AICA平滑肌细胞外向电流(+40 mV)的抑制率分别为(25.3 ± 7.1)%、(43.1 ± 10.4)%和(68.4 ± 3.9)%，对MA平滑肌细胞外向电流(+40 mV)的抑制率分别为(13.2 ± 5.6)%、(34.2 ± 4.0)%和(59.3 ± 7.3%)，相同钳制电压下，相同浓度的18βGA对两种微动脉平滑肌外向电流的抑制程度之间无明显差异。(3)预灌流10 mmol/L TEA能显著逆转18βGA对微动脉平滑肌细胞外向电流的抑制作用。上述结果提示豚鼠AICA和MA微动脉平滑肌细胞外向电流由电压依赖的K+通道(KV)和大电导钙激活K+通道(BKCa)介导，而18βGA能够浓度和电压依赖性地抑制该外向电流。

关键词： 微动脉; 平滑肌细胞; 18β-甘草次酸; 大电导钙激活钾通道; 膜片钳

分类号：R331.3

[18β-glycyrrhetinic acid inhibits outward current of vascular smooth muscle cells of arterioles.] [Article in Chinese]

MA Ke-Tao, LI Xin-Zhi, LI Li, ZHANG Zhong-Shuang, SHI Wen-Yan, SI Jun-Qiang^*

The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, 2Department of Physiology, School of Medicine, Shihezi University, Shihezi 832002, China

Abstract

The aim of the present study was to investigate the effect of 18β-glycyrrhetinic acid (18βGA) on the membrane current of vascular smooth muscle cells (VSMCs) in arteriole. Guinea pig anterior inferior cerebellar artery (AICA) and mesenteric artery (MA) were isolated, and single VSMCs were harvested using digestion with papain and collagenase IA. Outward currents of the VSMCs were recorded by whole-cell patch clamp technique. Results were shown as below: (1) 1 mmol/L 4-AP and 1 mmol/L TEA both could partially inhibit the whole-cell current of VSMCs in arterioles. (2) 18βGA inhibited the outward current of VSMCs in a concentration-dependent manner. The inhibitory rates of 10, 30 and 100 μmol/L 18βGA on the membrane current of VSMCs (+40 mV) were (25.3 ± 7.1)%, (43.1 ± 10.4)% and (68.4 ± 3.9)% respectively in AICA, and (13.2 ± 5.6)%, (34.2 ± 4.0)% and (59.3 ± 7.3)% respectively in MA. There was no significant difference between the inhibitory effects of 18βGA on AICA and MA. 18βGA also inhibited the outward current of VSMCs in a voltage-dependent manner. 18βGA induced a more pronounced inhibition of the outward current from 0 to +40 mV, especially at +40 mV. (3) With the pretreatment of 10 mmol/L TEA, the inhibitory effect of 18βGA on the membrane current of VSMCs was significantly abolished. These results suggest that the outward current of VSMCs in arterioles is mediated by voltage-dependent K+ channels (KV) and big conductance calcium-activated K+ channels (BKCa), which can be inhibited by 18βGA in concentration- and voltage-dependent way.

Key words: arteriole; smooth muscle cell; 18β-glycyrrhetinic acid; big conductance calcium-activated potassium channel; patch clamp

收稿日期：2011-03-31　　录用日期：2011-08-22

通讯作者：司军强　　E-mail: sijunqiang11@hotmail.com

引用本文：

马克涛, 李新芝, 李丽, 张忠双, 石文艳, 司军强. 18β-甘草次酸抑制微动脉平滑肌细胞外向电流[J]. 生理学报 2011; 63 (6): 549-554.

MA Ke-Tao, LI Xin-Zhi, LI Li, ZHANG Zhong-Shuang, SHI Wen-Yan, SI Jun-Qiang. [18β-glycyrrhetinic acid inhibits outward current of vascular smooth muscle cells of arterioles.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (6): 549-554 (in Chinese with English abstract).