中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
8期
1081-1084,1085
,共5页
李超红%陈依春%翟旭雯%封启龙
李超紅%陳依春%翟旭雯%封啟龍
리초홍%진의춘%적욱문%봉계룡
内向整流钾通道%扎考必利%静息电位%延迟后除极%触发活动%异丙肾上腺素%心律失常
內嚮整流鉀通道%扎攷必利%靜息電位%延遲後除極%觸髮活動%異丙腎上腺素%心律失常
내향정류갑통도%찰고필리%정식전위%연지후제겁%촉발활동%이병신상선소%심률실상
inward rectifier potassium current%zacopride%resting membrane potential%delayed after-depolarizations%triggerd activity%isoproterenol%ar-rhythmias
目的：观察内向整流钾通道( I K1通道)激动剂扎考必利(zacopride,Zac)对异丙肾上腺素(isoproterenol,ISO)诱发大鼠心律失常的抑制作用及其机制。方法①利用麻醉状态大鼠体表心电图观察Zac对ISO诱发心律失常的效应；②利用细胞内微电极技术观察Zac对大鼠右心室乳头肌细胞静息电位及ISO联合高钙诱发延迟后除极( DADs)和触发活动( TA)的效应。结果① ISO组大鼠出现频发室性期前收缩及ST段下移；与之相比, ISO+Zac组大鼠室性期前收缩的发生率从100%降至50%(n=6,P<0．05),1 h内室性期前收缩的个数从1574±521降至33±40(n=6,P<0．05)。② Zac(1μmol·L-1)使正常大鼠右心室乳头肌细胞静息电位从(-74．42±1．95)mV 增加至(-78．50±2．07)mV(n=6,P<0．05)。③ Zac(1μmol·L-1)可明显抑制ISO联合高钙诱发的大鼠右心室乳头肌 DADs 和 TA,使其发生率从93．75%降至25%(n =16,P <0．05),且这一作用可被1μmol·L-1 BaCl2反转。结论选择性IK1通道激动剂扎考必利可明显抑制ISO诱发的室性心律失常,其机制与它增强I K1,使膜电位负值增大和抑制延迟后除极有关。这一结果进一步支持适度增强I K1是一条可行的抗心律失常途径。
目的：觀察內嚮整流鉀通道( I K1通道)激動劑扎攷必利(zacopride,Zac)對異丙腎上腺素(isoproterenol,ISO)誘髮大鼠心律失常的抑製作用及其機製。方法①利用痳醉狀態大鼠體錶心電圖觀察Zac對ISO誘髮心律失常的效應；②利用細胞內微電極技術觀察Zac對大鼠右心室乳頭肌細胞靜息電位及ISO聯閤高鈣誘髮延遲後除極( DADs)和觸髮活動( TA)的效應。結果① ISO組大鼠齣現頻髮室性期前收縮及ST段下移；與之相比, ISO+Zac組大鼠室性期前收縮的髮生率從100%降至50%(n=6,P<0．05),1 h內室性期前收縮的箇數從1574±521降至33±40(n=6,P<0．05)。② Zac(1μmol·L-1)使正常大鼠右心室乳頭肌細胞靜息電位從(-74．42±1．95)mV 增加至(-78．50±2．07)mV(n=6,P<0．05)。③ Zac(1μmol·L-1)可明顯抑製ISO聯閤高鈣誘髮的大鼠右心室乳頭肌 DADs 和 TA,使其髮生率從93．75%降至25%(n =16,P <0．05),且這一作用可被1μmol·L-1 BaCl2反轉。結論選擇性IK1通道激動劑扎攷必利可明顯抑製ISO誘髮的室性心律失常,其機製與它增彊I K1,使膜電位負值增大和抑製延遲後除極有關。這一結果進一步支持適度增彊I K1是一條可行的抗心律失常途徑。
목적：관찰내향정류갑통도( I K1통도)격동제찰고필리(zacopride,Zac)대이병신상선소(isoproterenol,ISO)유발대서심률실상적억제작용급기궤제。방법①이용마취상태대서체표심전도관찰Zac대ISO유발심률실상적효응；②이용세포내미전겁기술관찰Zac대대서우심실유두기세포정식전위급ISO연합고개유발연지후제겁( DADs)화촉발활동( TA)적효응。결과① ISO조대서출현빈발실성기전수축급ST단하이；여지상비, ISO+Zac조대서실성기전수축적발생솔종100%강지50%(n=6,P<0．05),1 h내실성기전수축적개수종1574±521강지33±40(n=6,P<0．05)。② Zac(1μmol·L-1)사정상대서우심실유두기세포정식전위종(-74．42±1．95)mV 증가지(-78．50±2．07)mV(n=6,P<0．05)。③ Zac(1μmol·L-1)가명현억제ISO연합고개유발적대서우심실유두기 DADs 화 TA,사기발생솔종93．75%강지25%(n =16,P <0．05),차저일작용가피1μmol·L-1 BaCl2반전。결론선택성IK1통도격동제찰고필리가명현억제ISO유발적실성심률실상,기궤제여타증강I K1,사막전위부치증대화억제연지후제겁유관。저일결과진일보지지괄도증강I K1시일조가행적항심률실상도경。
Aim To investigate the inhibitory effects of zacopride(Zac) on arrhythmia induced by isoproterenol ( ISO) and the underlying mechanisms in rats. Meth-ods ①ECGs were recorded in anesthetized rats in vi-vo to observe the effects of zacopride on arrhythmia in-duced by ISO. ② Intracellular microelectrode tech-nique was used to investigate the effects of zacopride on resting membrane potential, delayed afterdepolariza-tions ( DADs) and triggered activity ( TA) induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ven-tricular papillary muscle of rats. Results ① In ISO group rats, ventricular premature beats ( VPB ) oc-curred frequently with ST-segment depression. Com-pared with ISO group, the incidence of VPB in ISO+Zac group decreased from 100% to 50% ( n=6 , P<0. 05 ) and the total number of VPB recorded in 1 hour significantly reduced from 1 574 ± 521 to 33 ± 40 ( n=6,P<0. 05). ② Zacopride at 1 μmol·L-1 could hy-perpolarize the resting membrane potential of right ven-tricular papillary muscle in normal rat from ( -74. 42 ± 1. 95 ) mV to ( -78. 50 ± 2. 07 ) mV ( n =6 , P <0. 05). ③ Zacopride at 1 μmol·L-1 significantly de-pressed the DADs and TA induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ventricular papilla-ry muscle. The incidence of DADs decreased from 93. 75% in rats in ISO group to 25% in ISO +Zac group ( n =16 , P <0. 05 ) , and this antiarrhythmic effect could be reversed by 1 μmol·L-1 BaCl2 . Conclusions Zacopride, a selective IK1 channel ago-nist , can significantly inhibit cardiac arrthymia induced by ISO in rats, the mechanism of which is mainly at-tributed to zacopride-induced hyperpolarization of the resting membrane potential and subsequent suppression of DADs and TA via enhancing IK1 . These results pro-vide further evidence that to enhance IK1 moderately may be a feasible pathway for antiarrthymic therapy.
