摘要
目的：探讨青蒿素抗心律失常的离子电流基础。方法：用全细胞膜片钳技术和双电极电压钳技术。结果：当细胞超极化到－１００ｍＶ时，青蒿素以浓度依赖方式明显抑制家兔心室肌细胞Ｉｋ１，５０μｍｏｌ·Ｌ－１青蒿素可使家兔心室肌细胞Ｉｋ１从对照组的－２３６±０３９ｎＡ减少到－１４３±０３１ｎＡ。给予非洲蛙卵母细胞注射Ｋｉｒ２．１ｃＲＮＡ后，用不同浓度青蒿素灌注，可减低Ｋｉｒ２．１钾通道电流，此作用呈电压和浓度依赖性。青蒿素对Ｋｉｒ２．１钾通道的阻断作用呈可逆性。结论：青蒿素能有效抑制离体心肌细胞Ｉｋ１，其抗心律失常作用机理与其抑制心肌细胞Ｉｋ１及阻断Ｋｉｒ２．１通道电流有关。
AIM: To determine the ionic basis of antiarrhythmic action of artemisinin. METHODS: The effects of artemisinin on the inward rectifier K current ( I k1 ) in isolated rabbit myocytes were studied using whole cell voltage clamp technique, and its effects on the cloned inward rectifier K channels (K ir2.1 ) expressed in xenopus oocytes were investigated by two microelectrode voltage clamp technique. RESULTS: In rabbit myocytes, artemisinin significantly decreased I k1 in a concentration dependent manner. Artemisinin (50 μmol·L -1 ) decreased I k1 from -2 36±0 39 nA to -1 43±0 31 nA ( P <0 05, n =6 ) at -100 mV. Artemisinin reduced the current of K ir2.1 channel in xenopus oocytes in a dose dependent and voltage dependent manner when artemisinin was perfused with different concentration after K ir2.1 cRNA was injected. The blockade effect of artemisinin on K ir2.1 channel was revertible. CONCLUSION: Artemisinin inhibited effectively I k1 in isolated rabbit myocytes. The mechanism of antiarrhythmic action of artemisinin may be related to its inhibition on I k1 and blockade of K ir2.1 channel current.
出处
《药学学报》
CAS
CSCD
北大核心
1999年第8期569-572,共4页
Acta Pharmaceutica Sinica
基金
黑龙江省杰出青年基金
